CR EOYS2 Flashcards
What pathology should you investigate after an ECG after a TIA? [1]
arrhythmias
Name two clinical signs of CO2 retention [2]
- Flap (asterixis): ask a patient to extend arms out, close eyes, should be able to hold for 30 secs
- Bounding pulse
A patient suffering from an asthma attack would use which of the following
Simple face mask
Nasal cannulae
Venturi mask
Face mask with reservoir bag
A patient suffering from an asthma attack would use which of the following
Simple face mask
Nasal cannulae
Venturi mask
Face mask with reservoir bag
A patient suffering from an sepsis attack would use which of the following
Simple face mask
Nasal cannulae
Venturi mask
Face mask with reservoir bag
A patient suffering from an sepsis attack would use which of the following
Simple face mask
Nasal cannulae
Venturi mask
Face mask with reservoir bag
Label A & B [2]
A: Lung failure
B: Pump failure
LEARN ! Name 4 reasons that could cause hypoventilation
Increased resistance as a result of airway obstruction (e.g.COPD)
Reduced compliance of the lung tissue/chest wall (e.g. pneumonia, rib fractures, obesity).
Reduced strength of the respiratory muscles (diaphragm) (e.g. Guillain-Barré, motor neurone disease)
Drugs acting on the respiratory centre reducing overall ventilation (e.g. opiates)
Name three consequences of CO2 retention [3]
State for each their clinical signs [3[
End-organ hypoxia
- Altered mental status
- Bradycardia and hypotension (late)
Haemoglobin desaturation
- Cyanosis
CO2 Retention
- Flap (asterixis): ask a patient to extend arms out, close eyes, should be able to hold for 30 secs
- Bounding pulse
Explain MoA of how atherosclerosis causes ischaemic stroke
Endothelial damage allows lipoproteins and monocytes to adhere to the vessel wall and enter the intima.
Monocytes differentiate into macrophages and engulf the lipoprotein and become known as foam cells.
Further accumulation of cholesterol and foam cells forms a fatty streak.
Foam cells release pro-inflammatory cytokines which leads to smooth muscle cell proliferation. and connective tissue to deposition in the fatty streak.
These changes form a fibrous cap over the lipid core.
A necrotic core can form due to the lack of capillaries.
Plaque rupture removes the endothelium which exposes the fibrous cap leading to thrombosis and occlusion of the artery
What are the 3 overlying causes of cellular death in stroke? [3]
Mechanical compression
Cerebral Oedema
Excitotoxicity
How would you treat acute ischameic stroke:
- if within 4.5 hrs of onset [1]
- if outside 4.5 hrs of onset [1]
Thromboylsis:
- using drug - Alteplase
- Must occur within 4.5 hours of onset
- haemorrhage has to be excluded
Mechanical thrombectomy
- endovascular removal of a thrombus from a large artery.
Histopathological features of adenocarcinoma? [3]
irregular, closely packed glands effacing normal lung appearance with atypical cells lining the gland lumen
glandular hyperplasia
desmoplastic (fibrotic) stroma around them.
Describe that immune pathophysiology of granuloma formation
- Antigen taken up by macrophage & presented to CD4+ helper T cells
- CD4+ helper T cell convert to TH1 subtype
- TH1 cells screte IL-2 and INy
- T cell proliferation and macrophage activation
- Macrophages and T cells secrete TNFa
- Causes increase in inflammatory cells
- Causes repeat of TH1 cells screte IL-2 and INy etc
A patient’s investigations reveal pancytopenia and macrocytosis. His peripheral smear shows hyper-segmented neutrophils. Serological tests reveal positive anti intrinsic factor antibodies. What other biochemical derangements might be observed in this patient?
A. Increased plasma metanephrines
B. Elevated ferritin levels
C. Increased urinary 5-hydroxytryptamine
D. Elevated plasma homocysteine
A patient’s investigations reveal pancytopenia and macrocytosis. His peripheral smear shows hyper-segmented neutrophils. Serological tests reveal positive anti intrinsic factor antibodies. What other biochemical derangements might be observed in this patient?
D. Elevated plasma homocysteine
This patient likely has megaloblastic anemia due to a deficiency of vitamin B12. Vitamin B12 is an essential co-factor involved in two important enzymes. One of these enzymes is methionine synthase, which converts homocysteine to methionine. The deficiency of cobalamin will lead to the impaired functioning of this enzyme. This will result in an accumulation of homocysteine which can be detected in the blood.
Explain what bundle branch block is [1]
Which part of ECG can see bundle branch block occur in? [1]
Explain what bundle branch block is [1]
Disruption to the electrical signal that causes your heart to beat [0.5]
Causes altered pathways for depolarisation [0.5]
Which part of ECG can see bundle branch block occur in? [1]
Prolongs QRS
Which views of the heart are seen by each type of ECG lead on a standard 12-lead ECG? [4]
- *S**eptal: V1, V2
- *A**nterior: V3, V4
- *L**ateral: V5, V6, AVL, I
- *I**nferior: II, III, AVF
AVR: neutral
Eccentric hypertrophy:
- Caused by? [4]
- Characterised by? [2]
Eccentric hypertrophy:
Caused by? [1]
- Aortic and mitral regurgitation
- Systolic dysfunction (loss of cardiac inotrophy
- -Volume overload (hypervolaemia due to ventricular or renal failure)
- Alcohol / cocaine
Characterised by? [2]
- Chamber dilation - lumen gets bigger, wall gets smaller: cant contract properly
Which of the following forms the ventricular outflow tracts?
Truncus ateriosus Bulbus cordis Sinus venosus Primitive ventricle Primitive atria
Which of the following forms the ventricular outflow tracts?
Truncus ateriosus **Bulbus cordis** Sinus venosus Primitive ventricle Primitive atria
Which structures of the heart are formed from the bulbus cordis?
The smooth outfow of the left and right ventricles. The muscular right ventricle. The muscular intraventricular septum.
How would you ID acute myeloid leukemia? (AML)
- A heterogeneous population of myeloblasts with cells ranging from small to medium-sized to large. Note presence of a few maturing myeloid elements.
- Large myeloblasts with prominent nucleoli. Maturing myeloid elements i.e. neutrophils or eosinophils.
How would you ID chronic lymphocytic leukemia (CLL) from PBS and BMS?
- PBS: Mature-appearing lymphocytes with high nuclear to cytoplasmic ratios, with scant agranular cytoplasm and homogeneously condensed chromatin without nucleoli. Characteristic “soccer ball’ chromatin pattern. Numerous smudge cells
- BMS: tissue is displaced by nodular and interstitial aggregates of clonal B cells.
How would you ID chronic myeloid leukemia (CML) from PBS and BMS?
PBS: > 100K white blood cells with neutrophilia, significant increase in metamyelocytes and myelocytes, also basophilia and eosinophilia
BMS: increased granulocyte precursors, basophils, eosinophils and occasionally monocytes
Normal erythroid compartment, variable pseudo Gaucher cells and sea blue histiocytes, increased reticulin fibres
What condition is shown here?
Upper Lobe Blood Diversion
Due to the increased pressures, blood is pushed upwards creating a ‘stag antler’ appearance. Blood is diverted as fluid is more likely to build up lower down due to gravity and cause relative hypoxia and vasoconstriction, thus the blood is diverted to the upper zones.
In the midline of this film, we can also see several sternal sutures.
Explain the mechanism of iron absorbtion and transport in the body for haem iron and non haem iron
Haem iron
- Haem iron – (highly bioavailable) absorbed through DMT1
- Fe removed from Haem. Can then be stored as ferritin OR can exit cell through Ferroportin
Non-haem iron:
- Mostly in the form of Fe3+, but only Fe2+ can be absorbed by the enterocyte. Enzyme reductase: Fe3+ à Fe2+
- Enters via DMT1
- Fe removed from Haem. Can then be stored as ferritin OR can exit cell through Ferroportin
Then transferrin transports Fe3+ around body
What is the first committed cell in erythropeoisis? [1]
What is the pathway from Haematopoietic stem cell (HPSCs) - to erythrocyte? [1]
What is the first committed cell in erythropeoisis? [1]
Proerythroblast
Haematopoietic stem cell (HPSCs) –> common myeloid progenitor cell –> (CMPC)Proerythroblast –> erythroblast –> reticulocyte – > erythocyte
The proerythroblast develops into an (early) erythroblast. The erythroblast then undergoes a sequence of changes where its nucleus progressively shrinks and its cytoplasm becomes filled with haemoglobin (not stained). When full of haemoglobin it is called a normoblast. The normoblast then expels its nucleus and becomes a reticulocyte. Most reticulocytes stay in the marrow and mature into erythrocytes but some may be released into the blood, especially after haemorrhage. Reticulocytes can transport oxygen, just not as efficiently as mature erythrocytes. They can mature into adult RBCs in the circulation
What is anaemia of inflammation / chronic disease caused by? [3]
Why will iron supplementation not help in patients with this condition?
What is anaemia of inflammation?
IL-6 released and causes:
* more hepcidin: which blocks release of Fe2+ out of via ferroportin
* blocks production of EPO (& therefore rbc production)
* inhibits production of rbc in bone marrow
Why will iron supplementation not help in patients with this condition?
Problem is with iron being absorbed in gut and iron getting out of macrophages, along with depressed erythropoietin release and erythropoiesis caused by inflammatory cytokines – need to treat cause inflammation
Explain how B12 [1] and folate deficiencies [1] would affect the NS?
Which pathology would B12 deficiency lead to if left untreated? [1]
- Folate deficiency: neural tube defects
- B12 deficiency: demylination
if not treated can lead to: subacute combined degeneration of the cord
Degeneration of posterior and lateral columns of spinal cord: TEST FOR WITH ROMBERG SIGN
Treatment for folate deficiency? [1]
Treatment for vitamin B12 deficiency:
- pernicious anaemia? [1]
- alternative causes? [1]
Folate: oral folic acid
B12:
- for pernicious anaemia: hydroxycobalamine IM (NOT ORAL). be aware of hypokalaemia due to increased K+ requirement as erypoesis increase back to normal
- other: Oral cyanocobalamine
What is pernicious anaemia caused by?
Autoimmune antibodies to parietal cells (sensitive) or IF (specific) – destroy or inactivate IF: SO:
Decreased or absent Intrinsic factor (IF) causes progressive exhaustion of B12 reserves.
How can folate mask B12 defiency?
Elevated intake of folic acid alleviates anaemia caused by B12 deficiency by providing a continual supply of active folate (otherwise B12 needed to regenerate active folate via methionine synthase). BUT irreversible neurological sequelae B12 deficiency may still occur!
Name & explain 2 inherited defects that cause haemolyitc anaemia, arising from enzymes? [2]
Pyruvate Kinase Deficiency:
- Causes deficiency in pyruvate kinase in erythrocytes: final step in glycolysis
- Less energy for ATPase pump – cells lose K+ & H20, dehydrate and are destroyed - haemolysis
Pentose Phosphate Pathway: Glucose-6-phosphate dehydrogenase (G6PD) deficiency:
- NADPH required to keep glutathione in reduced state – major cellular anti-oxidant
- Pentose phosphate pathway is only source of reduced glutathione in RBC – so RBCs very affected when exposed to oxidative stress
- Increased oxidative stress from infection or drugs (examples, sulfa drugs, primaquine) or certain foods (one example, fava beans) will cause haemolysis
Haemolytic anaemias:
Explain how can get aquired damage to RBC?
Microangiopathic haemolytic anaemia: from mechanical damage:
- stress from passing through heart valves
- cells snag on fibrin strands
- heat damage
- osmotic damage (drowing in freshwater)
ALL TYPES OF INTRAVASCULAR HAEMOLYSIS
GO OVER THE CYCLE in lecture
Which of the following acts a receptor for von Willebrand Factor (vWF)
P2Y12
COX-1
TXA2
Glycoprotein Ib
Which of the following acts a receptor for von Willebrand Factor (vWF)
P2Y12
COX-1
TXA2
Glycoprotein Ib
This diagram depicts platelet adhesion to endothelium
Which of the following is VWF
A
B
C
D
This diagram depicts platelet adhesion to endothelium
Which of the following is VWF
A
B
C
D
glycoprotein IIb/IIIa (GPIIb/IIIa) an integrin complex found on platelets. It is a receptor for fibrinogen[1] and von Willebrand factor and aids platelet activation. The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence
This diagram depicts platelet adhesion to endothelium
Which of the following is fibrinogen
A
B
C
D
This diagram depicts platelet adhesion to endothelium
Which of the following is fibrinogen
A
B
C
D
This diagram depicts platelet adhesion to endothelium
Which of the following is GpIIb/IIIa
A
B
C
D
This diagram depicts platelet adhesion to endothelium
Which of the following is GpIIb/IIIa
A
B
C
D
This brusing would indicate
VWD
Factor deficiency
This brusing would indicate
VWD - small / multiple
Factor deficiency - one large bruise
Why does vein wall pathology increase chance of DVT / PE?
How can vein wall pathology / damage occur? [3]
Heparan sulfate projects out of the endothelial wall. These projections prevent platelet adhesion to intact endothelial membrane. If damaged - less heparan sulfate:
- increases risk of clot formation, especially if combined with reduced blood flow
Vein wall pathology can occur from:
a) smoking / alchohol
b) diabetes
c) chronic inflam disease (RA)
How do you diagnose DVT?
Use Wells’ Score:
- Add up points on the score: 2 points or more is likely. 1 is unlikely
- If 2 or more score: have proximal leg vein ultrasound
i) have positive scan - give treatment
iI) have negative scan, repeat in 6-8 days - do a D Dimer test
a) if D-dimer is positive: repeat scan in 6-8 days
b) if second sacan D-dimer is negative - consider alternative disease, but discuss symptoms with patient so they can look out for it - Venography - gold standard
* o D-dimer is fibrin degradation product
o Is a marker of fibrin formation
o Raised in VTE and other pathologies
D dimer: fibrin degradation product released when thrombus is degraded by by fibrinolysis low D dimer = low DVT risk.
Why might someone have hypercoaguable blood? [3]
When would you consider hypercoagulable states for DVT?
Why might someone have hypercoaguable blood?
- Antithrombin deficiency
- Protein C or S defiency (anti-coagulant proteins)
- Factor V Leiden mutation :causes resistance to activated protein C
Consider when no obvious signs for VTE/ PE
How would you investigate for PE?
Classification system? [1]
ECG? [3]
CXR? [1]
ABG [1]
o Wells Score greater than 4
ECG - sinus tachycardia, right heart strain. T-wave inversion on anterior leads (V1-V3). Classic finding: S (deep S wave in lead I), Q ( present in lead III) and T (inverted T in lead III).
o CXR- possible small pleural effusion, peripheral wedge shaped density above diaphragm, focal oligemia. Most common finding with PE patients is a normal CXR, but used to excludes other diagnoses
o ABG - often hypoxic, low CO2 (due to hyperventilation)
Explain mechanism of how heparin works to treat PE [3]
Name a drug that is a synthetic heparin [1]
Heparin binds to antithrombin and activates it; activated complex then inactivates factor Xa, preventing conversion of prothrombin to thrombin (thrombin converts fibrinogen into fibrin - integral step in clot formation)
Fondaprinux
What are specific treatments for pregnant; breast feeding and patients with cancer assosciated thrombosis? [3]
Specific treatments:
· During pregnancy:
o LMWHeparin throughout pregnancy - NOT warfarin or DOACs as they cross the placenta
During breast feeding
o LMWH and warfarin can be used.
Patient with cancer-associated thrombosis
o LMWH more effective than warfarin
o DOACs being evaluated.
What is the treatment if a STEMI is detected? [3]
Open the occluded artery as soon as possible to restore blood flow to the heart (Time is Muscle) (angioplasty) at heart attack centre. less than120 mins is aim
If can’t open artery via stent aim to thromboylse (but want to avoid because have high risk of bleeding).
Reperfusion therapy:
- Aspirin + ticagrelor or pragural (dual antiplatelets)
- Heparin
- PCI
How do you chose which antiplatelet should use for unstable angina, NSTEMI [3] or STEMI? [2]
Acute STEMI: Prasugrel & Aspirin
Unstable angina and NSTEMI who are having coronary angiography: Prasugrel or ticagrelor, as part of DAPT with aspirin
What are the two types of treatment for haemophilia? [2]
What type of medication can you give for haemophilia? [3]
Two types of treatment:
Prophylaxis
On-Demand
Medication:
Factor VIII/ IX- recombinant or plasma (IV)
Desmopresssin / DDAVP (S/C) - causes the release of von Willebrand’s antigen from the platelets and the cells that line the blood vessels where it is stored. Von Willebrand’s antigen is the protein that carries factor VIII.
Tranexamic Acid (IV and Oral) - Antifibrinolytic (stops fribrinlysis)
Symptoms of VWD? [6]
Frequent nose bleeds
Easy bruising
Gum bleeds (Teeth falling out & extractions)
Menorrhagia
Menstrual bleeding lasting more than 7 days
Intestinal/gut bleeding
Symptoms and their severity vary greatly
Explain the basic overview from vessel injury –> stable haemostatitc plug
- Vasoconstriction occurs to reduce blood loss
- Collagen released is also. This causes platelet released, which in turn causes release of serotonin, TXA ADP & platelet phospholipids.
- Serotonin then helps with vasoconstriction, whilst TXAADP helps with platelet aggregation.
- Together they help to make a primary plug
- Through vasoconstriction, shear stress is increased. This cause various molecules to be release, including VWF (important in platelets adhering to vessel walls)
- Simultaneously to vasoconstriction: tissues factor is exposed. This causes coagulation cascade.
- Platelet Phospholipid is the surface for many of the coagulation cascade that occurs.
- Thrombin is created fibrin
- together makes stable hameostatic plug
Give brief overview on how primary haemostasis occurs to make platelet plug
- Vessel injury causes collagen to be exposed
- VWF binds to collagen one side, and the otherside to platelets via glycoprotein 1b receptor
- Platelets become activated, start clump other platelets. Through glycoprotein IIb, IIIa and fibrin, form stable haemostatic plug.
Describe how the kidney reabsorbs bicarbonate if there is respiratory alkalosis
- Decreased carbonic anhydrase activity within the cell: less CO2 converted to bicarbonate and protons. Less protons in cell means less protons excreted by sodium-proton exchange ATPase in luminal wall into urine to be excreted.
- This results in less bicarbonate is converted to CO2 in tubule and filtered bicarbonate is excreted in urine
- Leads to decreased excretion protons and decreased bicarbonate reabsorption
Treatment of HACE [4]
Recognition!
Descend immediately
Dexamethasone orally or intravenously (prevents brain swelling)
Acetazolamide (reduces intracranial pressure by reducing cerebrospinal fluid volume)
Oxygen
Hyperbaric oxygen treatment (portable chambers now available)
Explain the mechansim of action of an ADP receptor antagonist [2]
Name three of the most common [3]
The ADP receptor antagonists bind to the P2Y12 receptor to prevent ADP-induced platelet activation
Clopidogrel
Prasugrel
Ticagrelor
Explain the mechanism of action of aspirin [3]
Non-selective for COX-1 and COX 2 enzymes (prevent aggregation)
COX 2 inhibition prevents arachidonic acid conversion to Thromboxane A2
Thus preventing Thromboxane A2 formation, preventing platelet aggregation.
Which of the following is a non-specific phosphodiesterase inhibitor
Heparin
Warfarin
Aspirin
Dabigatran
Dipyridamole
Which of the following is a non-specific phosphodiesterase inhibitor
Dipyridamole
Inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function
Name four DOACs [4]
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
Describe MoA of the DOACs:
Rivaroxaban
Apixaban
Edoxaban
Direct factor Xa inhibitor (more modern version of heparin)
Explain mechanism of action of Dabigatran [1]
Direct thrombin inhibitor
Which of the following is not a direct factor Xa inhibitor
Rivaroxaban
Apixaban
Edoxaban
Dabigatran
Which of the following is not a direct factor Xa inhibitor
Rivaroxaban
Apixaban
Edoxaban
Dabigatran: direct thrombin inhibitor
