Path - Blood and Clots - Exam 3 Flashcards
(105 cards)
1
Q
What is haemostasis?
A
Haemostasis is the human body’s response to blood vessel injury and bleeding. It involves a coordinated effort between platelets and numerous blood clotting proteins (or factors), resulting in the formation of a blood clot and subsequent stopping of the bleed.
Balance between clot formation (thrombin) and clot lysis (plasmin)
2
Q
What occurs in a bleeding phenotype and clotting phenotype?
A
Bleeding:
- increased clot lysis
- decreased clot formation
Clotting:
- decreased clot lysis
- increases clot formation
3
Q
What is it about vascular endothelium injury that affects haemostasis? I.e. what triggers it?
A
Following injury there is:
- smooth muscle vasospasm – constriction of blood flow and reduced production of prostacyclin and NO which usually prevent platelet adherence.
- exposure of collagen – initiator of platelet activation (initiates intrinsic coagulation pathway)
- exposure of tissue factor – thrombin generation (initiates extrinsic coagulation pathway)
4
Q
What triggers constriction of blood flow on vascular endothelium injury?
A
- direct injury to vascular smooth muscle
- chemical release by endothelial cells/platelets
- reflexes triggered by nociceptors
5
Q
What is primary hemostasis and what are the steps involved?
A
Platelet plug is formed to rapidly stop the initial bleeding after injury. Short term control of bleeding.
- platelet adhesion
- platelet shape change
- granule release
- recruitment
- aggregation (hemostatic plug)
- SECONDARY – permanent plug
6
Q
What is secondary hemostasis and what are the steps involved?
A
Secondary hemostasis is the process where the platelet plug initially created in primary hemostasis is reinforced by the conversion of fibrinogen to fibrin. Long-term control.
- factor cascade
- fibrin-cross linking at site of injury
7
Q
What is fibrinolysis and what are the steps involved?
A
The breakdown of clots
8
Q
What causes platelet activation and what do they do once activated?
A
Circulating platelets bind sub-endothelial matric proteins through surface receptors, i.e. collagen and tissue factor.
Once activated they:
- change shape – to form platelet plug and formation of pseudopods to mediate adherence
- release granules (ADP, fibrinogen vWF etc). Some recruit more platelets, fibrinogen starts clot formation.
- express fibrinogen receptor
9
Q
What mediates ‘bridge’ formation between platelets and what mediated platelet adhesion?
A
Bridge
- Fibrinogen receptor
- GP IIb/IIIa
- Fibrinogen binds platelets together via receptor
Adhesion:
- von Willebrand factor (vWF)
- binds to collagen and GP1b/IX/V receptors
10
Q
What are the key roles of platelets?
A
- adhesion/aggregation to form the primary hemostatic plug
- release okatelt-activating and pro-coagulant molecules from granules
- provide a pro-coagulant surface for subsequent activity of the coagulation activity
11
Q
What are the steps in coagulation?
A
- initiation – vessel injury exposes TF – fibroblasts to circulating FVIIa in plasma. These form an active complex
- Vascular spasms
- Platelet plug formation:
- The TF-FVIIa complex activates other clotting factors – this generates small amount of thrombin localized to vascular defect
- Propagation:
a) Thrombin IIa activates:
- plateles
- coagulation proteins required for its own production
b) large scale production of thrombin occurs on platelet surface - Coagulation cascade leads to fibrin formation
- Fibrinogen converted to fibrin, which reinforces and stabilizes platelet plug
- Fibrinolysis activated to localize clot site and then to remove it when injury is healing
12
Q
What are the steps in fibrinolysis?
A
- plasminogen converted to plasmin
2. plasmin enzymatically degrades fibrin so clot can be removed
13
Q
What are the common features of a platelet defect vs clotting factor deficieny:
A
- Platelet Defect:
a) Excessive bleeding after minor cuts: YES
b) Petechiae: COMMON
c) Ecchymoses: SMALL/SUPERFICIAL
d) Haemarthroses, muscle haematoma: UNCOMMON
e) Bleeding with proceedures: OFTEN IMMEDIATE, VARIES IN SEVERITY
f) Bleeding phenotype: MUCOCUTANEOUS
- Clotting factor deficiency:
g) Excessive bleeding after minor cuts: NOT USUAL
h) Petechiae: UNCOMMON
i) Ecchymoses: MAY BE LARGE/EXTENSIVE
j) Haemarthroses, muscle haematoma: YES
k) Bleeding with proceedures: PROCEDURAL OR DELAYED
l) Bleeding phenotype: DEEP TISSUE BLEEDING
14
Q
What is important to ask about in clinical history for haemostasis disorder?
A
a) bleeding history
- timing
- triggers
- severity
b) drug use
c) family history
15
Q
What sort of things are screened for in the lab in coagulation disorders?
A
- platelet count
- prothrombin time (PT)
- activated partial thromboplastin time (APTT)
- +/- thrombin time (TT) and fibrinogen
- APTT – instrinsic pathway
- PT – extrinsic pathway
- TT – fibrinogen to fibrin
16
Q
How are coagulation assays performed?
A
Performed on plasma
17
Q
What does prothrombin time tell you?
A
- Evaluates extrinsic/common pathways:
- II, V, VII, X, fibrinogen
- Reference range established depending on test
- Relatively insensitive to heparin
- . High INR = a calculated value allowing for comparison of PT results between labs. Use as if PT.
18
Q
What does Activated partial thromboplastin time (APTT) time tell you?
A
- induces clot
- Evaluated FVII, IX, XI, XII
- Generally remains normal until a single factor is
19
Q
What does thrombin time (TT) tell you?
A
- measures conversion of fibrinogen to fibrin
- sensitive to inhibitors such as heparin
20
Q
What types of fibrinogen assays exist?
A
- functional – evaluates both quantity and quality
- diluted plasma clotted with very high concentration of thrombin
- reduces impact of inhibitors
- high dose thrombin – time independent of thrombin therefor just functional fibrinogen - immunological – quantity only
- use when functional abnormalities are suspected to get quantity
21
Q
What do you do if you get an abnormal assay result? (clotting)
A
- repeat, especially if unexpected or weird
- mixing studies:
- assay performed mixing patient plasma with 1:1 normal plasma
- correction to normal:
factor deficiency - failure to correct:
- suggests coagulation inhibitor
22
Q
What are some of the potential errors with coagulation assays?
A
- pre-analytical errors: can result in incorrect diagnosis or inappropriate management
- analytical
- post-analytical
23
Q
What are some of the pre-analytical errors that can occur with coagulation assays?
A
- sample volume
- sample handling
- storage – length and temp
- Patient factors:
- age
- gender
- blood group
- pregnancy
- stress/exercise
- anticoagulation
- other pathology
- diurnal
24
Q
What if lab results are normal but they have a history of bleeding?
A
Abnormalities in secondary haemostasis more or less excluded:
- moderate/severe factor deficiency unlikely if normal APTT/PT
- significant fibrinogen abnormality unlikely if normal Clauss fibrinogen
Abnormalities in primary haemostasis not excluded
- functional platelet abnormality
- other, i.e. von Willebrand disease
Test fibrinogen to compare Clauss (functional) and antigenic fibrinogen. If normal, do von Willebrand studies (FVIII and vWF)
25
What would you suspect if everything but APTT was normal (APTT high), but on mixing the APTT becomes normal? What if treatment is effective, but then patient comes back and APTT is still high, and this time remained high on mixing?
Clotting factor deficiency. Common = haemophilia
Treatment: factor replacement
Loss of response to previously effective factor replacement and non-correction on mixing suggests:
Acquired factor inhibitor
Reason: typically alloimmune phenomenon against recombinant FVIII.
26
With APTT, what will mixing tell you?
1. If mixing study full corrects….
- suspect factor deficiency
- VII, IX, XI, XII
2. If non-correction…
Evaluate bleeding phenotype
a) if bleeding – factor studies (especially VIII) +/- inhibitor assay
b) if clotting – test antiphospholipid antibodies
27
What would you suspect if someone has a high PT, high APTT and low fibrinogen? How would you check?
Fibrinogen issue. Tests Clauss (functional) and Antigenic fibrinogen independently. If they have low Clauss fibrinogen, this suggests dysfibrinogenaemia (functionally abnormal fibrinogen)
28
What would you suspect if someone has high haemaglobin and haematocrit, and high PT and APTT?
Test error – citrate:plasma ratio is high. Repeat collection with lower citrate dose is likely to show a normal result.
29
What are the components of blood
- 55% plasma
- 45% erythrocytes
-
30
What are two automated test methods for doing a full blood count?
a) Aperture Impedance
| b) Light Scatter (laser)
31
How is haemoglobin measured?
NOT measured by cell sorter
- RBCs lysed and light absorbance is measures
32
How is the Red Cell Count measured?
number of cells through light source
33
How is the Hematocrit measured?
– measures % of blood taken up by red cells
| - summation of number of pulses and average pulse height
34
What is the RDW (Red Cell Distribution Width)?
Red Cell Distribution Width (RDW)- measure of the range of variation of red blood cell (RBC) volume
i) RDW-SD – when reported as standard deviation
- calculates the wide at the 20% height levels of the histogram to find MCV
ii) RDW-CV – when reported as coefficient of variation
- reference range = 11.5-14.5%
35
How are reticulocytes singled out for automated measures?
Why are they measured?
Can target RNA with dye as reticulocytes have more RNA than mature RBC.
Measurement used to check for:
- anaemia
- increased in haemolysis/acute bleeding
- BM failure/CRF/B12/fol/Fe deficiency
36
How are white cells distinguished from red cells to measure white cell count?
What are some potential errors that could occur despite this distinguishment?
RBCs are discriminated from platelets by size and then lysed.
```
Potential errors:
- large platelets
- white cell agglutination
- NRBCs (nucleated RBCs)
What are some factors that could cause bad results for RCC or WCC?
```
37
What are the 5 different white blood cells that can be measured in a WCC and how are they distinguished from each other?
Can get 5 part differential:
- neutrophils
- lymphocytes
- monocytes
- eosinophils
- basophils
Differentiated by:
- volume
- complexity/light scatter
- fluorescence after labeling
38
What can the mean platelet volume tell you?
Younger platelets are smaller so can tell you about age
39
What are some factors that could cause bad results for RCC or WCC?
- cold agglutinants - increases MCV and MCHC
- lipemia - high lipid levels causes turbidity and increases Hb and MCH
- Nucleated RBCs - will be counted as white cells
- High WCC - can result in high Hb, RCC and RBC indices
- platelet clumps - decreases platelets but increases WCC
40
What 2 factors cause cytopaenias (low cell counts)?
a) lower production
| b) higher destruction
41
What are the 3 broad categories of anemia?
a) Microcytic - presence of small, often hypochromic, red blood cells in a peripheral blood smear and is usually characterized by a low MCV (small and pale).
- Iron deficiency
- thalassemia
- chronic disease
- rare causes
b) Macrocytic – large RBCs
- megaloblastic (B12 or folate deficiency) and non-megaloblastic
c) Normocytic – normal MCV, but decreased Hb and hematocrit.
- BM Failure
- Haemolysis
42
What are some of the clues in blood of iron deficiency?
- thrombocytosis (too many platelets)
- low RCC
- high RDW (RBC volume)
- Blood film: pencils, elliptocytes, target cells.
43
What are the symptoms of thrombocytopenia? (platelet deficiency)
- Oozing and bruising
- Purpuras
- Cutaneous mucosal bleeding
- Prolonged bleeding from wounds
- Menorrhagia
- Internal bleeds – rare until less than 10.
44
What are the causes of thrombocytopenia? (platelet deficiency)
a) Failure of platelet production, i.e. BM failure, selective megakaryocyte depression and hereditary problems
b) Increased destruction:
- drug induced
- DIC or TTP: microangiopathic process (Disseminated intravascular coagulation and Thrombotic thrombocytopenic purpura)
- immune – alloantibodies (neonatal and transfusion) or autoantibodies
45
What are the two categories of lymphocytosis (increased lymphocytes) and neutrophilia?
- clonal (all the same, i.e. cancer) vs reaction
- reactive tends to look more variable and has more cytoplasm
- reactive – viral, stressors, shock etc
- neutrophilia is usually reactive
46
What are the intrinsic and extrinsic pathways of the coagulation cascade?
a) intrinsic = long one initiated by surface contact (collagen)
b) extrinsic = short one initiated by tissue damage (tissue factor)
47
What is thrombosis?
Intra-vascular coagulation of blood in life. Can be physiological or pathological.
48
Describe the factors that favour the formation of thrombi
Virchow’s triad:
1. injury to endothelium
- loss of repellent action of endo cells
- exposure of underlying collagen and tissue factor
2. Alteration in blood flow
a) Stasis:
- decreases laminar flow
- blood elements settle out and build up
b) turbulence
- loss of laminar flow
- blood elements damaged against vessel wall
3. Alteration in blood composition (hypercoagulable state)
- change in concentration or function of clotting factors
49
What are some of the morphological features of thrombi?
Lines of Zahn – alternating lines of lighter color (platelets and fibrin) and darker layers (RBCs)
Propagation – grow
Head and Tail – head is firmly attached to wall and tail extends toward the heart
Mural – thrombus attached to the wall
Occlusion – 100% blocked
50
What are the potential outcomes for a thrombus?
First it will propagate (grow).
Then it will either:
a) resolve (fibrinolytic pathway)
b) organize and re-canalize (macrophages, fibroblasts and endothelial cells)
c) embolize (break off and travel) – process of restoring flow with holes
- it can actually become infected if patient has bacteraemia/scepticaemia
51
What are the broad clinical effects of thrombi?
a) Arteries:
- block inflow to organs/tissue
- ischemia and infarction
b) Veins:
- block outflow from tissues
- congestion, oedema, extravasation
- +/- ischemia
52
What factors effect the impact of a thrombus?
- type of bessesl (artery vs vein)
- degree of obstruction (partial vs complete)
- tissue or organ supplies
- speed of onset
- presence of collateral circulation
- timing of thrombolytic therapy
53
What are the sites of clinical importance with thrombi?
• Heart
- aneurysms (cause thrombus)
- valves (i.e. artificial valve replacement)
- rheumatic fever
- endocarditis
• Aorta
- atheroma (causes thrombus, also called atherosclerosis)
- aneurysm
• Arteries
- heart
- gut ischemia
- brain
- lower limbs ischemia/gangrene
• Capillaries
- crush injuries
- burns
• Veins
deep calf veins – prone to embolize, especially to lung
• Disseminated intravascular coagulation
54
Define ischaemia, infarction and infarct.
Ischaemia – reduction in blood flow to an organ or tissue
a) reversible
b) irrversible
Infarction – the ischaemic death of tissue within the living tissue
Infarct – localized area of necrosis in an organ or tissue resulting from an inadequate blood supply
a) haemorrhagic characteristic of tissues with a dual blood supply
b) Pale/Ischaemic necrosis – interruption of inflow (bloodless)
55
What are the possible causes of infarction?
1. Occlusion of arterial supply (commonest)
- in situ thrombosis (at site it formed at)
- embolus
- arterial spasm
- arterial disease without thrombosis
- external occlusive pressure
2. Venous occlusion
- in situ thrombosis
- mechanical occlusion (i.e. hernia)
3. Occlusion of tissue capillaries (and other small vessels)
- frostbite
- fat embolus
- decompression sickness
- external pressure as in bedsores
- sickle-cell anemia
- chronic myeloid leukaemia
- antigen-antibody complex reaction
- disseminated intravascular coagulation
56
What factors are the consequences of ischaemia dependent on?
1. Architecture of blood supply – collateral circulation?
2. Rate of development of occlusion
3. Completeness of occlusion
4. Duration of occlusion
5. Tolerance of tissues to anoxia
6. General state of the blood and cardiovascular system (oxygenation, BP etc)
57
What are the possible effects of ischemia?
- no effect
- functional effect (i.e. angina, cardiac arrhythmia)
- focal cellular degeneration +/- necrosis
- atrophy (waste away)
- replacement fibrosis
- circumscribed necrosis = INFARCTION
58
What are the constitutional (systemic) effects of infarction?
- fever
- leukocytosis
- raised ESR (erythrocyte sedimentation rate)
- release of enzymes and other proteins into blook
- AST
- CK
- LDH
- Cardiac Troponins T and I
59
Describe the morphological features of infarction.
General:
- microscopic changes after 6 hours
- macro 12-24
- Surrounding inflammation – few days
- Red/pale are with haemorrhagic border by 1 week
- Serousal fibrinous exudate if lesion extends to surface
- Macrophages devour products of cell breakdown
- Slow progressive ingrowth of granulation tissue
- Subsequent fibrosis +/- dystrophic calcification
- Infection may convert area to abscess (septic infarct)
- Final outcome dependent on regenerative potential of necrotic tissue
60
What is the cause, factors, morphology and consequences of ischaemia in the heart?
Usual cause:
Coronary artery atherosclerosis with plaque rupture and subsequent thrombosis
Factors to consider:
- no regeneration in myocardium – heals by fibrosis
- there is only small interarterial anastomoses – ineffectual, but may expand if occlusion occurs slowly
Might see:
- Myocardial infarction:
- pale area of coagulative necrosis surrounded by haemorrhagic border (coagulative necrosis preserves architecture of dead tissue)
- Healed (fibrotic) MI
- Microscopic level – necrotic muscle fibers show nuclear loss and early disintegration, may see inflammation
Consequences:
- angina (partial occlusion)
- MI
- Arrhythmia
- ECG change and abnormal enzymes
- Aneurysm
- Cardiac rupture
- Reperfusion injury
- Mural thrombus
- Fibrous scarring
- Cardiac aneurysm
61
What is the cause, factors and consequences of ischaemia in the brain?
Usual cause:
Arterial thrombosis or embolism
Factors to consider:
- ganglion cells die within minutes
- no regenerative capacity
Consequences:
- pale or haemorrhagic
- Rapid liquefactive necrosis
- Gliosis
- Compound granular corpuscules
62
What is the cause and consequences of ischaemia in the lungs?
Usual cause:
Pulmonary embolus from from leg veins, pelvis or right atrium
Dual blood supply (pulmonary and bronchial arteries) – may prevent infarct if small vessel obstructed
Consequences:
- massive pulmonary embolus (sudden death without infarction)
- pulmonary infarction (only ~10%)
- pulmonary hypertension – rare
- no effect
63
What could cause ischaemia in the kidney?
a) General renal ischaemia:
- proximal tubular necrosis
- renal cortical necrosis
b) Local ischaemia:
- atheroma
- thrombosis
- embolus
64
What is the cause, factors and consequences of ischaemia in the intestine?
Cause:
- *Usually mechanical obstruction, i.e. hernia or volvulus resulting in venous compression
- Venous thrombosis
- Mesenteric artery disease
If gradual – ischaemic colitis maybe. Otherwise necrosis, i.e. gangrene.
65
What are the diagnostic criteria for an acute myocardial infarction (heart attack)?
Typical rise and/or fall of a cardiac biomarker (preferably troponin) with at least one value above the 99th percentile, and at least one of the following:
1. Ischemic symptoms
2. Development of Q waves on ECG
3. New ECG changes of ischemia (ST elevation or depression)
4. Imaging evidence of new loss of viable myocardium
5. Identification of intracoronary thrombus by angiography or autopsy
66
Why is troponin used as the recommended biomarker for Myocardial Infarctions?
- Troponin is central to the definition of acute myocardial infarction – patients can have negative elevated CK-MB levels even if they have suffered an AMI (Acute myocardial infarction).
- Greater diagnostic window - Due to slow release of Troponin, it is detectable in the blood for several days. CK-MB is cleared rapidly.
- Greater specificity than CK-MB - Certain isoforms of Troponin I and T are only found in heart muscle
67
What causes elevation of cardiac troponin?
Most of the troponin within the myocyte is found in the structural elements of the cell, so when necrosis occurs there is a steady leaching of troponin into the circulation.
68
What are some examples of reasons for elevated troponin in the absence of MI?
- age
- renal failure
- extreme exertion during exercise
- certain medications
- being stabbed
- many more
69
What were some of the previous biomarkers used?
- CK-MB – however many people suffer an AMI without elevated CK-MB levels. It also has a narrower diagnostic window than troponin.
- AST (aspartate transaminase) was the first used, however it is not specific for heart damage - use for liver function test instead
- LDH (lactate dehydrogenase) – low specificity
- Myoglobin – low specificity
70
What causes elevated CK?
- Exercise – very common. Usually improved in 3-5 days.
- Muscle injury – trauma, ischemia, shock, burns
- Renal failure
- alcohol – binge drinking or chronic overuse
- endocrine problems
- myopathies (disease of muscle tissue)
- electrolyte disorders
- medications
71
What are the liver function tests?
- total bilirubin
- alkaline phosphatase
- y glutamyl transferase
- alanine aminotransferase (‘transaminase’ or ALT)
- aspartate aminotransferase (AST)
- total protein
- albumin
- globulin
72
What are common causes of elevated transaminase levels?
- NAFLD (non-alcoholic fatty liver disease)
- alcohol
- viral hepatitis
- medications
- hemochromatosis
- coeliac disease
- non-hepatic
73
What are the transaminase rules of thumb?
Transaminase = ALT
Aspartame aminotransferase = AST
ALT usually > AST
- If AST > 2x ALT – think alcohol or cirrhosis.
- Alcohol does not usually cause ALT >5x normal.
- NAFLD ~2-4x
- viral hepatitis can be >20x if acute, often 2-3x in chronic C, and 2-15x in Chronic B
- Ischemia – VERY elevated. If >ALT 1500 consider ischemia.
74
What are some of the patterns of liver dysfunction?
a) Cholestasis (Jaundice) – bile cannot flow from the liver to the duodenum, therefore expect high bilirubin.
b) Enzyme induction – increased production of y glutamyl transferase in the liver.
c) Hepatic – high alanine aminotransferase
75
What would you typically see for NAFLD?
high y glutamyle transferase and high alanine aminotransferase
76
What would you suspect if a patient has only mildly elevated bilirubin but nothing else suspicious?
Gilbert’s syndrome
77
Do most lipid accumulations remodel the artery outwards or inwards?
Outward remodeling of the artery.
Luminal stenosis (inwards) tends to occur late in the process, and there can be considerable atheroma without significant luminal narrowing.
78
For arterial lesions, what is the best predictor of rupture?
The fibrous cap thickness
79
What are most Acute Coronary Syndromes caused by?
NOTE: Acute coronary syndrome is a term used for any condition brought on by sudden, reduced blood flow to the heart.
Rupture of the fibrous cap. Thrombosis occludes the remaining artery.
80
What is the link between Acute Coronary Syndromes and shear stress?
Atheroma is not deposited evenly around the arteries. Areas of low shear stress are more likely to be responsible for ACS.
81
What are the types of emboli?
1. Solid
- thombo-emboli
- athero-emboli
- tumour emboli – usually venous
- bone marrow emboli – usually venous
- foreign body emboli (i.e. fungus) – usually venous
2. Liquid
- fat emboli
- amniotic fluid emboli
3. Gaseous
- air emboli
- nitrogen emboli
82
What are the sources of emboli in the systemic circulation?
- thrombo-emboli
- athero-emboli
```
From:
A) Arterial
- atherosclerosis
- arterial fibrillation
- endocarditis
- MI
- Aneurysm
```
B) Venous
- deep vein thrombosis
83
What tissue/anatomical sites are particularly prone to certain emboli?
Solid emboli:
a) arterial circulation
- head and neck
- upper limbs
- kidneys, gut, spleen
- *lower limbs – 75%
b) venous system
- systemic: pulmonary arterial system: stops blood from R heart going to lungs, therefore increased pressure on R ventricle and ventilation-perfusion mismatch.
- portal: liver
c) lymphatic system
84
What are the effects of a pulmonary embolus?
a) Main pulmonary artery at bifurcation
- if >60% blockage – acute R heart failure – sudden death
b) Larger branch
- pulmonary haemorrhage
- +/- infarct
c) Smaller branch
- pulmonary haemorrhage +/- infarct
- nothing
d) Multiple smaller branches
- chronic pulmonary hypertension
- Right heart failure
85
What happens to an embolus?
```
Solid: Athero or thrombo:
a) lysis (dissolves)
b) develops superimposed thrombosis
c) becomes organized and re-canalized – incorporate into vessel wall resulting in thickening of wall and narrowing of lumen. Obstruction causing diminished or absent blood flow.
Tumor – metastasis
Foreign body – infection
```
86
What causes a fat embolus and what are the effects?
Causes:
- multiple fractures
- injury to subcutaneous tissues
Mechanism of injury:
a) biochemical injury – free fatty acids are toxic to endothelium
b) mechanical obstruction (lesser)
Fat embolism syndrome:
a) pulmonary insufficient
- tachopnoea
- SOB
- tachycardia
b) neurologic symptoms
- irritability
- restless – coma
c) diffuse petechial rash
d) thrombocytopaenia due to platelet destruction
- haemorrhage
- anaemia
87
What causes an amniotic fluid embolus and what are the effects?
Occurs during childbirth into uterine veins. Acute or chronic effects, including death or coma.
88
What causes an Air (gas) embolus and what are the effects?
Causes:
- operation
- injections
- laparoscopy
- pneumothorax
Collects in R heart acting as a physical obstruction and interferes with RV function.
89
What causes a Nitrogen (gas) embolus and what are the effects?
Causes:
N dissolved into blood under pressure comes out of solution when the pressure drops quickly
- scuba divers
- glider pilots etc
- physical obstruction
Effects:
- joints
- brain
- heart
- Caissons Disease (chronic bends in joints)
90
Necrosis may be described as “The spectrum of morphological changes which follows death of cells or tissues”. What other criterion is essential to accurately define necrosis?
The changes of necrosis occur in a living organism.
91
List 3 important metabolic aberrations which commonly result from cell injury due to ischaemia.
Three of: Reduced oxidative phosphorylation, failure of sodium pump, influx of water and Na+, loss of K+, influx of Ca+ reduced glycogen synthesis, reduces protein synthesis
92
Occlusion of arterial supply commonly results in ischaemia. List 3 causes of arterial occlusion.
Arterial thrombosis, embolus, vascular spasm, vascular disease without thrombosis eg atherosclerosis. Also external compression (uncommon)
93
Apart from arterial occlusion, name two other abnormalities which may result in ischaemia?
Venous occlusion and occlusion of small vessels including capillaries
94
list two common causes of venous occlusion
- in situ thrombosis
- Mechanical occlusion eg hernia (veins
compressible)
95
list 3 common causes of occlusion of small vessels
- frostbite
- fat embolus
- external pressure
96
The effects of ischaemia may vary from ‘no clinical or pathological effect’ to sudden death of the affected individual. Name three other possible outcomes of ischaemia.
Functional effects such as angina, arrhythmia, reversible or irreversible cell injury, atrophy, fibrosis etc
97
List 4 variables which determine the outcome of occlusion of vascular supply to an organ or tissue.
Architecture of blood supply, rate of development, completeness and duration of occlusion, tolerance of tissues to ischaemia, systemic factors (general state of circulation)
98
What is the first microscopic morphological change that you will see as a result of infarction following ischaemic injury?
Nuclear pyknosis
99
What are the morphological effects of infarction following ischaemic injury?
- Microscopic changes after 6 hrs
- Macroscopic changes 12-24 hrs
- Surrounding inflammation after a few days
- By 1 week, well developed red area or pale area with haemorrhagic border (inflammation)
- Serosal fibrinous exudate if lesion extends to surface
- Macrophages devour products of cell breakdown
- Slow progressive ingrowth of granulation tissue – ‘organization’
- Subsequent fibrosis (scarring), +/- dystrophic calcification
- Infection may convert area to abcess (septic infarct)
- Final outcome dependent on regenerative potential of necrotic tissue
100
How may blood tests facilitate a diagnosis of infarction?
Raised white cell count, raised ESR (erythrocyte sedimentation rate), measurement of enzymes released into the blood
101
Name two ‘functional’ consequences of coronary artery narrowing.
Angina, cardiac arrhythmia
102
Cardiac aneurysm is a late complication of myocardial infarction. What are the two most serious consequences of cardiac aneurysm likely to cause serious morbidity or mortality in an affected patient.
Heart failure. Source of thrombo-embolus to other organs.
103
What changes are likely to be seen in the brain of a patient who dies 5 years following a large cerebral infarct?
Usually an old cerebral infarct will appear as a cavity, (the result of liquefactive necrosis) often with surrounding gliosis
104
What changes are likely to be seen in lung tissue of a patient who dies suddenly (‘drops dead’) from massive pulmonary embolus?
There will be no changes within the lung tissue directly due to the embolus as the morphological changes of infarction take hours to develop. Of course the thrombo-embolus will be visible in the pulmonary artery/trunk, together with any pre-existing lung disease.
105
What is the likely pathological outcome of:
a. Complete occlusion of the inferior mesenteric artery?
b. Gradual occlusion of the inferior mesenteric artery?
a. Infarction of the bowel
| b. Ischaemic colitis
