Pathology 1 + 2 Flashcards
(71 cards)
1
Q
What percentage of population are hypertensive?
A
25% - 1 in 4
2
Q
Why are repeat measurements for hypertension important?
A
Normal variation in individuals at different times of day
3
Q
What is white coat hypertension?
A
Raised blood pressure due to fear when visiting doctor
4
Q
Complications of hypertension? (5)
A
- Cardiac failure
- cerebral haemorrhage
- atheroma
- renal failure
- sudden cardiac death
5
Q
Epidemiology of hypertension?
A
- Incidence varies between countries
- Higher in black populations
- Lower in South Pacific
- Runs in families
- Rises with age
6
Q
What are 2 ways to classify hypertension?
A
- Aetiological (according to cause)
* Clinicopathilogical (according to consequences)
7
Q
What are aetiological classifications of hypertension? Clinicopathological?
A
- Primary (no known cause) and secondary (known cause)
* Benign (often primary) and malignant (often secondary)
8
Q
What happens to blood velocity at arterioles? Why? What happens when arterioles are damaged?
A
- Decreases
- Due to resistance
- BP will rise
9
Q
What is an example of a drug used to treat hypertension?
A
ACE-Inhibitors
10
Q
What is primary hypertension? Incidence?
A
- No obvious cause
* 90% of cases
11
Q
What are possible causes of primary hypertension? (5)
A
- Genetic factors (twin studies)
- Salt intake -25% salt sensitive hypertension
- Protein intake
- Renin - Angiotensin system
- Sympathetic activity (as BP = CO x SVR)
12
Q
What is salt sensitive hypertension? What can put you more at risk of salt sensitive hypertension? How is it controlled?
A
- Increase in dietary salt leads to increase in BP
- Genetic polymorphisms
- Controlled by reduced salt diet
13
Q
In renal disease, what is the hypertension?
A
Salt sensitive
14
Q
What is secondary hypertension? Causes? (5)
A
- Underlying disease (cause) is implicated
- Renal disease
- Endocrine disease
- Aortic disease
- Renal artery stenosis
- Drug therapy - steroids
15
Q
What are renal causes of secondary hypertension?
A
- Any renal disease (renal artery stenosis, acute or chronic glomerulonephritis, chronic pyelonephritis, cystic diseases, interstitial nephritis)
- reduced renal blood flow
- excess renin release
- salt and water overload
16
Q
What is chronic pyelonephritis?
A
Dysfunction of ureters, leading to disruption to renal blood flow and hypertension
17
Q
What are endocrine causes of secondary hypertension? Examples? (3)
A
Adrenal gland hyperfunction / tumours
- Conn’s syndrome - excess Aldosterone
- Cushing’s syndrome - excess corticosteroid
- Phaeochromocytoma - excess noradrenaline (due to tumour in adrenal gland
18
Q
Other causes of secondary hypertension?
A
- Coarctation of the aorta - congenital narrowing of segments of the aorta
- Drugs - including corticosteroids
19
Q
What is benign hypertension? How is it diagnosed?
A
- Cause of serious life threatening morbidity
* Asypmtomatic, incidental finding often health checks
20
Q
What are complications of benign hypertension? (5)
A
- Left ventricular hypertrophy
- Congestive cardiac failure
- Increases atheroma
- Increases aneurysm rupture - aortic dissection, Berry aneurysms (catastrophic brain haemorrhages)
- Renal disease
21
Q
What are the effects of hypertension on the heart? (8)
A
- Left ventricular hypertrophy
- Increased LV load
- Poor perfusion
- Interstitial fibrosis
- Micro-infarcts
- Diastolic dysfunction
- Arrhythmias
- Cardiac failure
22
Q
What are the effects of left ventricular hypertrophy? (3)
A
- Sudden cardiac death (due to arrhythmia and poor perfusion)
- Cardiac failure
- Affects outcome of other disease
23
Q
What are the effects of atherosclerosis in the aorta?
A
Can become rigid due to calcification so unable to stretch to receive systolic impulse
24
Q
What is aortic dissection?
A
- Hypertension damages tunica intima
* Endothelial tear – blood enters and can split layers apart
25
What is a subarachnoid haemorrhage? Caused by?
* Uncommon type of stroke caused by bleeding on the surface of the brain
* Rupture of berry aneurysm caused by benign hypertension
26
What is the risk of MI with benign hypertension? Stroke?
* Every 10mmHg of diastolic pressure above 85 doubles risk of MI
* Every 8mmHg of diastolic pressure above 85 doubles risk of stroke
27
Does hypertension only affect large vessels? What is this?
* No, can cause microvascular injury
| * Blood vessel wall changes in small arteries and arterioles
28
What vessels are usually affected in microvascular injury? Effects of microvascular injury? (2)
* Retina and kidney
* Thickening of media (smooth muscle)
* Hyaline atherosclerosis (plasma proteins forced into vessel wall making vessels rigid)
29
What sign can be looked for in the kidney to diagnose hypertension?
Hypertensive arteriosclerosis
30
What is malignant hypertension? What does it develop from? Why is malignant hypertension so urgent?
* Serious life-threatening condition where diastolic pressure >130
* Can develop from either benign primary or secondary hypertension ( ‘accelerated’ hypertension), or arise de-novo
* Needs urgent treatment to prevent death from stroke etc
31
Complications of malignant hypertension? (5)
* Cerebral oedema - seen as papilloedema (swelling of optic disc)
* Acute renal failure
* Acute heart failure
* Headache and cerebral haemorrhage
* Fibrinoid necrosis and endarteritis proliferans of blood vessel walls
32
What can be seen in microscopy when viewing afferent arteriole of kidney in patient with malignant hypertension? (4)
* Onion-skinning (swirling mass of endothelial cells)
* No lumen
* Haemorrhage
* Fibrin deposition in vessel wall
33
What is pregnancy-associated hypertension? Complications?
* Common - up to 10% of pregnancies
* Increased maternal and foetal morbidity and mortality
* Pre-eclampsia
* Eclampsia (resolve following birth/surgical removal)
34
What is the treatment for pre-eclampsia? Eclampsia? What can cause hypertension associated with pregnancy?
* C-section (resolve following deliver)
| * Hypertension in pregnancy can occur secondary to silent renal or systemic disease
35
What is a thrombus? An embolism?
* Abnormal mass of coagulant formed from flowing constituents within circulation
* Abnormal mass of coagulant (in solid, liquid or gaseous state) that travels within circulation and can impact vessels
36
What is ischaemia? Infarction?
* Ischaemia - reduction in tissue/organ perfusion
| * Infarction - ischaemic necrosis
37
What is a clot? What is the difference between a clot and thrombosis? (2)
* A coagulum of blood
* Clot occurs from bleeding outside circulation and is not an active process
* Thrombosis occurs within blood vessels and is an active, controlled process
38
Where can thrombosis occur? (3) What is this known as?
Anywhere but is favoured locations with the following:-
* Sites of endothelial injury
* Turbulent blood flow
* Hypercoagulable blood
Virchow's Triad
39
What is thrombosis? What 2 things are required to form a thrombus? (2)
Intravascular coagulation
* Platelet activation
* Fibrin production via coagulation cascade
40
What is the effect of platelet activation? (2)
* Attract and aggregate with other platelets
| * Aggregate with fibrin
41
What is the end point of the coagulation cascade?
Fibrin
42
Explain the platelet activation pathway (6)
* Endothelium lost (e.g. due to damage) so underlying collagen exposed
* Collagen binds to glycoprotein Ia/IIb on platelets
* Von Willebrands Factor (vWF) also binds to glycoprotein Ia/IIb
* Increases integrin expression on platelets allowing aggregation
* Glycoprotein IIa/IIb binds fibrinogen
* Activated platelets release granules to attract other platelets e.g. vWF, platelet activating factor (PAF), thromboxane A2 (TXA2) and ADP
43
What granules are released by activated platelets? (4) What is their purpose?
* vWF, platelet activating factor (PAF), Thromboxane A2 (TXA2), ADP
* To attract other platelets
44
What are the 2 pathways of the coagulation cascade? What does the intrinsic pathway start with? Extrinsic?
* Intrinsic and extrinsic
* Hageman factor (FXII) and kalikrien
* Tissue factor
45
What happens in the extrinsic pathway of coagulation cascade? How is intrinsic pathway measured? Extrinsic?
* Tissue factor joins factor VII (commonest pathway)
* Prothrombin Time (PT)
* Activated Partial Thromboplastin Time (APTT)
46
What is the common pathway of both the intrinsic and extrinsic pathways in coagulation cascade? (2)
* Factor Va and Xa activate factor IIa (thrombin)
| * Factor IIa and XIII then convert fibrinogen into insoluble fibrin (end point of coagulation cascade)
47
What is vitamin K required for with regards to coagulation pathway? What is vitamin K? Therefore, what happens in liver disease?
* Required to make factors II, VII, IX and X
* Fat soluble vitamin stored in the liver
* Liver disease stops production of factor II, VII, IX and X
48
What is the effect of Warfarin with regards to the coagulation pathway?
Stops production of II, VII, IX and X
49
What can cause endothelial injury? (6)
* Hypertension (turbulence)
* Toxins
* Infectious agents
* Smoking
* Autoimmune disease (primary vasculitis)
* Previous DVT
50
When will thrombosis occur in arterial system? Why will thrombosis not occur in arterial system normally?
* When there is underlying atherosclerosis
| * Arterial system is high flow so pro-coagulant materials are washed along before being able to do anything
51
What is atherosclerosis? What sites on an artery are more predisposed to endothelial damage?
* Formation of plaques at sites of endothelial damage
| * Sites where arteries branch as there is turbulent flow and hence increased endothelial damage
52
How can atherosclerosis lead to thrombus formation?
Surfaces of atheromatous plaque very thin so can rupture and cause thrombus formation
53
What are sites commonly affected by atherosclerosis/thrombosis/emboli? (5)
* Brain (cerebral infarction i.e. stroke)
* Carotid arteries (TIAs and strokes)
* Heart (MI, cardiac failure)
* Aorta (aneurysms -rupture causes sudden death)
* Legs (peripheral vascular disease with intermittent claudication)
* Feet etc (gangrene)
54
What are complications of atherosclerosis?
* Thrombosis
| * Narrowed coronary artery (stable angina)
55
What is stable (exercise-induced) angina? Unstable?
* Stable - coronary artery narrowed by atherosclerosis
| * Unstable angina - plaque ruptures causing thrombosis and large occlusion of coronary artery
56
What is primary vasculitis? What is it causative of?
* Autoimmune disease charactersied by inflammation directed at vessel walls (body attacks own blood vessels)
* Endothelial injury
57
What does turbulence cause? (2)
* Endothelial injury
| * Stasis
58
What is stasis? (2)
* Blood flow normally laminar with constituents in centre of vessel and slow plasma flowing peripherally
* Stasis is increased contact of platelets etc with vessel walls (no washing out) due to slow flow
59
Where does blood slow down? What does stasis normally occur as a result of?
* Deep venous system
| * Faulty valves and venous insufficiency (walls, etc) produce stasis
60
What are causes of hypercoaguability? Examples? (3)
Anything that causes increased viscosity
* Dehydration
* Polycythemia (increase in number of cells)
* Leukaemia
61
What is an example of a clot buster?
Plasmin
62
What are examples of anti-clotting proteins? (3) How do they work? (2)
* Protein C, protein S and antithrombin III
* Protein C and S - degrade factor V and VIII
* Antithrombin III - degrade II, IX and X
63
What is an example of an inherited disorder that causes hypercoaguability? What is this?
* Factor V Lieden
| * Mutation at point in factor V targeted by C and S protein
64
What are other inherited hypercoaguability disorders other than factor V Lieden?
* Protein C deficiency
* Protein S deficiency
* Antithrombin III deficiency
65
What are secondary causes of thrombosis? (8)
* Prolonged immobility
* Significant tissue injury (burns etc)
* Antiphospholipid syndrome (autoimmune)
* MI
* Atrial fibrillation
* Cancer
* Chemotherapy
* Marantic endocarditis
66
What are low risk secondary causes of thrombosis? (4)
* Contracetpive pill
* Smoking
* Renal disease (nephrotic syndrome)
* Cardiomyopathy
67
How does cancer cause thrombosis? Chemotherapy? Marantic endocarditis?
* Activate coagulation cascade through tumour produced TF, mucin, inflammatory cytokines
* Chemotherapeutic agents injure endothelium and increase risk of thrombosis
* Aseptic thrombotic endocarditis (thrombi form on heart valves)
68
What are other forms of embolism other than thromboembolism?
* Air (IV lines, etc)
* Septic (injecting drugs, abscess rupture)
* Amniotic fluid
* Tumour
* Fat (from bone marrow, gets into blood vessels usually from fractures)
69
What are the effects of lack of ATP? (2) What does this lead to? (5)
* Blocks Na/K/ATPase
* Ca channels (NCX1 blocked?) so increased intracellular calcium
* ATPase (makes things worse)
* Phospholipase (membrane damage)
* Proteases (membrane and cytoskeleton damage)
* Endonuclease (DNA damage and breakdown)
* Mitochondrial permeability (release pro death factors)
70
What are branching vessels that are at risk of endothelial injury (thus atherosclerosis)? What are organs distal to these branches at risk of? (2)
* Coronary vessels
* Above bifurcation of Aorta
* Origin and division of carotid arteries
* Renal arteries
* Superior Mesenteric Artery
Organs susceptible to embolism and infarction e.g. stroke, small bowel infarction
71
Why should caution be taken with drugs that lower blood pressure?
Do not want to lower DBP too much, as heart perfused during diastole
