Please enable JavaScript.
Coggle requires JavaScript to display documents.
CARDIOVASCULAR AND RENAL DISEASE - Coggle Diagram
CARDIOVASCULAR AND RENAL DISEASE
CARDIOVASCULAR PATHOLOGY
PATHOLOGY AND CLINICAL SIGNIFICANCE OF HYPERTENSION
Primary vs Secondary
Secondary causes
drugs
renal disease
primary aldosteronism
renovascular hypertension
obstructive sleep apnoea
pneumochromocytoma
cushing's syndrome
coarction of the aorta
Underlying pathophysiology
sodium and fluid balance, controlled by the kidneys
increased peripheral artery resistance
genetic factors - family history of hypertension
Induced pathophysiology
in small vessels, hypertension can cause hyaline or hyperplastic arteriosclerosis
hyaline arteriosclerosis is the homogenous, pink, hyaline thickening of the arteriolar walls with the loss of the underlying structural detail
hyperplastic arteriosclerosis is associated with malignant hypertension and it is the concentric laminated thickening of the arteriolar wall, hyperplasia and hypertrophy of the vascular smooth muscle cells, thickening of the basement membrane and deposition of fibrinoid material and necrosis of the vessel wall
in large vessels, hypertension accelerateds atherosclerosis
Complications of hypertension
Cardiovascular complications
atherosclerosis
aortic aneurysm
left ventricular hypertrophy and left ventricular failure
CNS complications
stroke
vascular dementia
Opthalmic complications
retinal haemorrhage and impaired vision
vitreous haemorrhage and retinal detachment
neuropathy of the nerves leading to extraocular muscle paralysis and dysfunction
Renal complications
chronic kidney disease
benign nephrosclerosis
PATHOLOGY OF ATHEROMA, ATHEROSCLEROSIS AND ANEURYSMS
Atherosclerosis is a chronic inflammatory and healing response of the arterial wall to endothelial injury and it is overall a dynamic process that can be focal or systemic
Atheroma lesion progression occcurs through
interaction between lipoproteins/lipids, macrophages and T lymphocytes with normal constituents of the vessel wall (including the endothelium and vascular smooth muscle cells)
ECM formation, angiogenesis and mineralisation
consequences of atheroma:
atherosclerotic stenosis
narrowing can lead to ischaemia
acute plaque change
rupture or haemorrhage into the plaque causing sudden expansion
thrombosis
with possible formation of an embolus
vasoconstriction
vascular ectasia (dilation)
structural weakness that can result in the forming of an aneurysm
characteristics of vulnerable/unstable plaques
thin fibrous cap (due to continuous remodelling)
large lipid cores
increased inflammation
adrenergic activity (from outside of the vessel wall)
types of aneurysms
true aneurysm - bounded by all arterial wall components
saccular - portion of the wall is involved e.g. a berry aneurysm
fusiform - diffuse circumferential dilation
false aneurysm - occurs through a breach in the vascular wall
extravascular haematoma that freely communicates with the intravascular space
lipid accumulation occurs through:
engulfing of lipids by macrophages and myointimal cells to form foam cells
extracellular and oxidised lipids accumulate and can cause further damage
ISCHAEMIC HEART DISEASE
Ischaemic heart disease is ischaemia of the myocardial tissue that results from an inadequate supply of blood and oxygen to a portion of the myocardium and it typically occurs when there is an imbalance between myocardial oxygen supply and demand
CAUSES OF IHD
due to the interactions of:
fixed atherosclerotic coronary artery narrowing
acute plaque change/disruption
vasoplasm/vasoconstriction of coronary artery
CLINICAL PRESENTATIONS OF IHD
angina pectoris
myocardial infarction
sudden cardiac death
chronic IHD with cardiac failure
CAUSES OF ACUTE PLAQUE CHANGE / DISRUPTION
plaque surface erosion or ulceration
rupture or fissuring of plaque
platelet aggregation and thrombus formation
haemorrhage into the plaque
vasospasm/vasoconstriction of the vessel wall
TYPES OF MYOCARDIAL INFARCTION
transmural
full thickness of heart wall
superimposed thrombus in atherosclerosis
focal damage
sub-endocardial
inner 1/3 to 1/2 of ventricular wall
decreased circulating blood volume
circumferential
CARDIAC FAILURE, CARDIOMYOPATHY, MYOCARDITIS
Congestive heart failure is the state in which the heart is inable to pump blood at the required rate and therefore the heart cannot maintain an adequate cardiac output
CAUSES OF CONGESTIVE HEART FAILURE
damaged myocardium due to severe ischaemia/infarct
obstruction to blood flow e.g. aortic stenosis, hypertension
regurgitant flow e.g. mitral or aortic valve regurgitation
cardiac conduction disorders e.g. heart block, arrhythmias
LEFT SIDED HEART FAILURE
CAUSES
ischaemic heart disease
hypertension
cardiac valve disease - aortic stenosis, mitral valve disease
myocardial disease
COMMON CLINICAL FEATURES
dyspnoea
orthopnoea - shortness of breath while lying flat
paroxysmal nocturnal dyspnoea
pulmonary congestion/oedema - crepitation on chest auscultation
pathomorphologically appears hypertrophied (adaptive) with dilated left ventricle and secondary enlargment of the left atrium
RIGHT SIDED HEART FAILURE
CAUSES
venous congestion syndrome that is usually a consequence of left sided heart failure due to increased pulmonary circulation pressure which puts pressure on the right side of the heart
COMMON CLINICAL FEATURES
splanchnic congestion - hepatosplenomegaly
peripheral oedema
pleural effusion
ascites - fluid accumulation in the peritoneal cavity
jugular venous distension and elevated jugular venous pulse
COR PULMONALE
pure right-sided heart failure that manifests due to the burdening of the right ventricle due to increased resistance of the pulmonary circulation
acute - in cases of a massive pulmonary embolism
chronic - due to chronic and severe pulmonary disorders
CARDIOMYOPATHY
TYPES OF PRIMARY CARDIOMYOPATHIES
dilated
hypertrophic obstructive
restrictive
arrhythmogenic right ventricular dyspnoea
a disease of the heart muscle
MYOCARDITIS
CAUSES
infectious
immune-mediated reactions
physical agents
sarcoidosis
VALVULAR AND CONGENITAL HEART DISEASE
THROMBOSIS AND EMBOLISM
A thrombus is a solid mass of blood constituents formed within the vascular system
An embolus is a mass of material in the vascular system which is mobile within a blood vessel and is capable of blocking it's lumen
Thrombophilia is an inherited or acquired defect of haemostasis leading to a predisposition to venous or arterial thrombosis
Virchow's triad is the inappropriate activation of normal haemostatic processes in an uninjured vessel or after a relatively minor injury and it involves:
intimal surface of vessels
pattern of blood flow
blood constituents - hypercoagulability
Arterial vs Venous thrombus
arterial thrombi are often occlusive whereas venous thrombi are almost invariably occlusive
arterial thrombi are usually superimposed onto atherosclerotic lesions
arterial thrombi cause an infarct distally
venous thrombi can form a long cast of the vessel lumen with many red blood cells
the majority of venous thrombi occur in the lower extremities
with venous thrombi, there is an increased risk of embolisation
SHOCK
CARDIOVASCULAR PHARMACOLOGY
PHARMACOLOGY OF ANTI-HYPERTENSIVE AGENTS
Malignant hypertension treatment = hospitalisation, administration of a parenteral vasodilatorr, beta-blocker and loop diuretic
BETA BLOCKERS
ACTIONS:
decrease sympathetic activity
gradual fall in arterial pressure
decreased cardiac output and renin release
SIDE EFFECTS:
bronchoconstriction
hypoglycaemia
bradycardia
cardiac failure
fatigue
depression
CLINICAL USES
hypertension with additional indications e.g. angina
hypertension in younger patients, i.e. below the age of 55
EXAMPLES:
1st generation (non-selective) = propanolol
2nd generation (beta1 selective) = atenolol
ACE INHIBITORS
EXAMPLES
sulfhydryl compounds e.g. captopril
phosphoryl agents e.g. fosinopril
carboxyl derivatives e.g. lisinopril
CONTRAINDICATIONS
pregnant women as it can lead to neonatal morbidity and mortality
SIDE EFFECTS
persistent dry cough due to increased bradykinin levels
poor renal perfusion in renal artery stenosis
hyperkalaemia
rash and taste disturbances can also occur with high dose captopril
DIURETICS
CALCIUM CHANNEL BLOCKERS
ACTIONS
binds to the alpha1 subunit of L-type calcium channels
decreased calcium entry into the cell
decreased intracellular calcium levels
generalised arterial vasodilatation (mainly affecting heart and smooth muscle)
SIDE EFFECTS
excessive vasodilation can lead to headaches, ankle swelling, and constipation
EXAMPLES
phenyl alkylamines e.g. verapamil
benzothiazepines e.g. dilitiazem
dihydropyridines e.g. nifedipine
The goals of hypertension management are:
reduce cardiac output
beta blockers
calcium channel blockers
reduce blood volume
diuretics
beta blockers
ACE inhibitors
reduce peripheral vascular resistance
vasodilators
ACE inhibitors
calcium channel blockers
ARBs
EXAMPLES
losartan
valsartan
INDICATIONS
if ACE inhibitors are contraindicated
no persistent dry cough as they have no effects on bradykinin levels
show slower progression in renal disease
ANGINA AND DYSLIPIDAEMIA TREATMENT
Drugs to reduce oxygen demand and/or improve coronary flow through reduction of BP, venous return and heart rate/force
NITRATES
MOA
Nitrates are metabolised into NO, which causes vascular smooth muscle relaxation, resulting in a decrease in cardiac work and oxygen demand
THERAPEUTIC EFFECTS
veno-relaxation and reduction in central venous pressure - reduced cardiac pre-load
relax arteries and reduces central aortic pressure - decrease in cardiac after load
coronary vasodilation - increase in coronary blood flow
diversion of blood from normal tissue to ischaemic myocardial tissue
SIDE EFFECTS
excessive vasodilation can cause
postural hypotension
headache/dizziness
relfex tachycardia
use in combo with a beta-blocker to combat this
tolerance to vasodilative effects
EXAMPLES
Nitroglycerin (GTN)
oral
short duration of action
Isosorbide mononitrate
slower duration of action
used more as prophylactic treatment
CALCIUM CHANNEL BLOCKERS
MOA
calcium channel blockers block L-type calcium channels through binding to distinct sites on these channels
THERAPEUTIC EFFECTS
decrease calcium ion entry into the cell and hence decrease intracellular calcium ion levels
vascular smooth muscle relaxation, decreased arteriolar pressure - affects after load
decreased cardiac contractility and heart rate
EXAMPLES
phenylalkylamines e.g. verapamil
used for arrhythmias
greater affect on the heart
benzothiazepines e.g. dilitiazem
dihydropyridines e.g. nifedipine and amlodipine
used for stable angina and hypertension
greater affect on smooth muscle
BETA BLOCKERS
Drugs that reduce plaque formation and ultimately slow the development of ischaemia
Lipid-Lowering Drugs
STATINS
MOA
inhibition of cholesterol synthesis in the liver
HMG CoA reductase inhibitors
inhibit the rate-limiting step in cholesterol synthesis
SIDE EFFECTS
rash
sleep disturbances
muscle aches
rhabdomyolysis
e.g. atorvastatin
irreversible inhibitor
long-lasting
PCSK9 INHIBITORS
MOA
monoclonal antibodies which prevent LDL receptor degradation in the liver
e.g. evolocumab
Drugs affecting platelet aggregation
underlying causes of angina:
consequence of atherosclerosis
diminshed coronary blood flow due to decreased diastolic aortic pressure or raised diastolic ventricular pressure
stenosis of the aortic valve
myocardial oxygen demand is greater than supply
The role of Lipoproteins in atherosclerosis development
damaged endothelium leads to moncyte recruitment and LDL is transported into the vessel wall
endothelial cells and monocytes generate free radicals
free radicals are taken up by macrophages leading to the formation of foam cells
foam cell formation triggers the release of pro-inflammatory cytokines and further plaque development occurs
Biological effects of Lipoproteins
HDL particles carry cholesterol away from peripheral tissues back to the liver for disposal - reverse cholesterol transport
LDL particles transport cholesterol from the liver to the rest of the body
VLDL particles are made in the liver and released into the circulation. They transport triglycerides and cholesterol from the GIT to adipose tissue
Overall management of atherosclerosis
LDL lowering through the use of statins
anti-hypertensive agents
lifestyle/dietary changes
surgical intervention
other: anti-inflammatories, HDL raisers, PCSK9 inhibitors
DRUG TREATMENT OF CARDIAC FAILURE
CLINICAL STAGES (NEW YORK CLASSIFICATION) OF HEART FAILURE
Class I - asymptomatic
Class II - compensated
Class III - decompensated
Class IV - refractory
TARGETS OF HEART FAILURE MANAGEMENT
haemodynamics
nitrates and vasodilators
positive inotropic drugs
neuro-hormonal control
ACE inhibitors
beta blockers
spironolactone
congestion
diuretics
positive inotropic drugs
THERAPEUTIC DRUG ORDER FOR MANAGEMENT OF HEART FAILURE
loop diuretics
ACE inhibitors
beta blockers
digoxin
nitrates/hyrdralazine
potassium sparing diuretics
POSITIVE INOTROPIC DRUGS
DIGITALIS (CARDIAC) GLYCOSIDES
e.g. digoxin
narrow therapeutic index
MOA:
blocks the sodium/potassium ATPase pump
reduced expulsion of cytosolic calcium which leads to increased intracellular calcium ion levels which results in increased contractility and cardiac output, and a slower heart rate
side effects:
neutropaenia
dysrhythmias
digitalis toxicity
excess inhibition of the sodium/potassium ATPase pump can lead to conduction problems and ventricular arrhythmia or tachycardia can occur
visual effects (if rhodopsin affected this can cause blurred vision/chromatopsia)
ADRENERGIC BETA RECEPTOR AGONISTS
PHOSPHODIESTERASE INHIBITORS
ANTI-ARRHYTHMICS
UNDERLYING MECHANISMS OF ARRHYTHMIAS
delayed after depolarisation
abnormal impulse conduction
ectopic pacemaker activity
heart block
drug induced
DIFFERENT TYPES OF ARRHYTHMIAS (based on site of origin of abnormality)
sinus node
sinus tachycardia
sinus bradycardia
sick sinus syndrome
atrium
atrial flutter
atrial fibrillation
supraventricular tachycardia
ventricle
ventricular ectopic beats
ventricular tachycardia
ventricular fibrillation
PURPOSE OF TARGETING CARDIAC ACTION POTENTIAL IN ANTI-ARRHYTHMIC TREATMENT
blocking conduction
altering action potential duration
preventing automaticity
DRUGS USED IN THE MODIFICATION OF ARRYTHMIAS
CLASS I - SODIUM CHANNEL BLOCKERS
e.g. procainamide
change the slope of the action potential during phase 0
CLASS II - BETA BLOCKERS
e.g. propanolol
decreases heart rate and conduction velocity
CLASS III - POTASSIUM CHANNEL BLOCKERS
e.g. solatol, amiodarone
increases action potential duration/effective refractory period and delays repolarisation
CLASS IV - L-TYPE CALCIUM CHANNEL BLOCKERS
e.g. verapamil
decreases conduction velocity in both SA and AV nodes
CLASS V - MISCELLANEOUS
e.g. ACE inhibitors, cardiac glycosides
decreases the automaticity of the SA node and slows conduction through the AV node
ANTI-PLATELET AGENTS, MI, STROKE
anti-platelet agents block different steps in the platelet activation pathway
COX-INHIBITORS
e.g. aspirin - stops platelet activation
block the enzymatic activity of the COX-1 enzymes
adverse affects include bleeding, stroke, and inhibition of gastric PGE2 can cause GI upset
BP should always be controlled due to it's affects on sodium and water retention
ADP RECEPTOR ANTAGONISTS
e.g. clopidogrel - acts as an anti-aggregant
e.g. ticagrelor - similar to clopidogrel, but faster acting
prevents ADP from binding to activated glycoprotein IIb/IIIa
adverse effects include similar bleeding effects to aspirin, alongside rash, diarrhoea, thrombotic thrombocytopaenic purpura and a small risk of neutropaenia
GLYCOPROTEIN IIb/IIIa RECEPTOR ANTAGONISTS
e.g. abciximab - acts as an anti-aggregant
prevents the binding of fibrinogen to activated glycoprotein IIb/IIIa
adverse effects include bleeding and thrombocytopaenia (immune mediated platelet destruction)
THROMBIN RECEPTOR ANTAGONISTS
e.g. Vorapaxar - blocks the cleavage of PAR-1
blocks the actions of thrombin
there is conflicting results over bleeding risks in regards to adverse effects
ANTI-COAGULANTS AND FIBRINOLYTICS
WARFARIN
MOA:
direct = blocks the reduction of vitamin K epoxide to vitamin K through the competitive inhibition of the epoxide reductase
indirect = inhibits the conversion of glutamic acid residue to carboxy-glutamic acid, essentially blocking the coagulation cascade at the precursor prothrombin to prothrombin (II) reaction
SIDE EFFECTS:
primary = increased risk of haemorrhage, impaired clotting factor synthesis in liver disease, andreduced clotting factors due to thyroxine increased warfarin efficacy in hyperthyroidism
secondary = warfarin can affect pregnancy in both the first and third trimesters, it can also cause warfarin-induced skin necrosis due to venule thrombosis
UNFRACTIONATED HEPARIN (UFH)
MOA:
increased activity of anti-thrombin III, and inhibits activated serine proteases (e.g. IIa, Xa) in the clotting cascade
SIDE EFFECTS:
bleeding
heparin induced osteopaenia - decreased bone formation
heparin induced thrombocytopaenia
VS LOW-MOLECULAR WEIGHT HEPARIN (LMWH)
LMWH has a shorter half life, superior bioavailability, and a reduced risk of adverse effects
FIBRINOLYTIC DRUG EXAMPLES:
STREPTOKINASE
RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR
RENAL PATHOLOGY
RENAL FAILURE AND CYSTIC RENAL DISEASE
CONSEQUENCES OF RENAL FAILURE
glomerular disease indicators:
microalbuminuria
proteinuria
nephrotic syndrome
haematuria
nephritic syndrome
general features:
abnormal bloods and urine
high blood pressure
oedema
non-specific, the body is being poisoned, symptoms - nausea and vomiting, malaise, fatigue, wasting
hypertension
anasarca (extreme oedema)
azotaemia (increased serum urea and creatinine)
uraemia (azotaemia with signs and symptoms)
malaise, aches and pains
fatigue and cognitive slowing
anorexia
nausea
weightloss/wasting
cardiovascular disease
serositis e.g. pericarditis
skin issues - itch, discolouration, dryness
neuropathy - peripheral parasthesia/numbness
susceptibility to infection
calcium and bone disease
acute kidney injury
sudden loss of renal function over days/weeks that is reversible
associated with a reduction in urine volume or a rise in serum creatinine
hyperkalaemia - volume overload, acidosis, hypernatraemia
uraemia
anuria/oliguria
polyuria
chronic kidney disease
structural abnormalities:
tumours
stones
infections
HEREDITARY KIDNEY DISEASE
autosomal dominant polycystic kidney disease
affects adults
genes affected are polycystin-1 on chromosome 16, and polycystin-2 on chromosome 4
autosomal recessive polycystic kidney disease
affects children
affected gene is fibrocystin
GLOMERULAR DISEASE PART I
MECHANISMS OF GLOMERULAR IMPAIRMENT
focal barrier rupture - haematuria
leakiness without rupture - proteinuria
impaired filtration - azotaemia
rupture and impaired filtration - nephritic syndrome
DIFFERENT POSSIBLE INSULTS TO THE GLOMERULUS
immune
immune complex mediated
type III hypersensitivity reactions
toxic and metabolic
diabetes mellitus
amyloidosis
vascular
hypertension
upstream vasculiitis
physical
hydrodynamic shear stress
high flow/filtration states
tubular pathology
perpetuation of glomerular damage - toxicity and ischaemia
FEATURES OF NEPHRITIC SYNDROME
haematuria (+/- proteinuria) - shows red cell casts
oedema - periorbital oedema in children
hypertension
+/- transient renal impairment (decreased GFR) - azotaemia (+/- uraemia)
IgA NEPHROPATHY
recurrent post-infectious haematuria
electron microscopy shows mesangial deposits
usually involves IgA and C3
ACUTE (DIFFUSE) PROLIFERATIVE GLOMERULONEPHRITIS
days/weeks post throat/skin infection (post-streptococcal infection)
children usually have asymptomatic haematuria
light microscopy shows increased cellularity and decresed capillary lumens due to endothelial swelling
usually involves granual IgG, IgM, and C3
subepithelial
GOODPASTURE'S SYNDROME
URTI-like illness
haemoptysis
lethargy
anti glomerular basement membrane antibodies
rapidly progressive glomerulonephritis with crescents
recurrence is possible if smoking habits continue
METHODS OF COMPLEMENT ACTIVATION
classical pathway - C3 and C4
alternative pathway - C3
mannose-binding lectin
EFFECTS OF COMPLEMENT ACTIVATION
leucocyte recruitment and activation
opsonisation
membrane attack complex
GLOMERULAR DISEASE PART II
TUBULOINTERSTITIAL AND TUBULAR PATHOPHYSIOLOGY
PATHOLOGY OF UTI AND RENAL CALCULI
RENAL TUMOURS
RENAL PHARMACOLOGY
DIURETICS
DRUGS AND RENAL FAILURE
DRUG-INDUCED NEPHROTOXICITY