u12W1: Hypertension Flashcards
What are the different hormones produces by the adrenal gland?
Cortex
Zona glomerulosa - aldosterone (mineralcorticoids)
Zone fasiculata - glucorticoids (some androgens)
Zona reticularis - androgens and some glucorticoids
Medulla - Catecholamines (noradrenaline and adrenaline)
What is the function of aldosterone?
Increase renal Na+ reabsoprtion
Increase K+ and H+ secretion.
What is the basic mechanism of adrenaline synthesis?
Tyrosine is converted to L-dopa by tyrosine hydroxylase
To dopamine by dopa decarboxylase (can be released from dopaminergic neurons)
Dopamine is converted to noradrenaline by dopamine beta hydroxylase (can be released from adrenergic neurons)
Converted to adrenaline by pheynylethanolone-N-methyltransferase (adrenal medulla)
Note adrenal medulla contains all three enzymes so can do all processes
Enzyme specific names are not important.
What are the common aetiologies of hypertension?
90% primary - idiopathic (no main cause)
10% - secondary hypertension.
What are the main categories are the pathogenesis of secondary hypertension?
What are some factors that may fit into this?
Endocrine- increased sympathetic tone
For example, primary hyperadlosteronism, pleochromocytoma, neuroblastoma,
Renogenic - often decreased renal blood flow or through renal parenchymal disease.
Diabetic Nephropathy, glomerularnephritis, embolic obstruction of the renal artery.
Cardiovascular - coarctaion of aorta, increased CO
Neurologic - sleep apnoea, increased intracranial pressure
Other cause: pre-eclampsia, oral contraceptives, monoamine oxidase inhbitors.
Describe four causes of secondary hypertension in detail.
Pre-eclampsia - abnormal development of placenta, failure to dilate spiral arteries, results in inflammatory protein released from plactena causing systemic vasoconstriction and increased renal fluid and salt retention
Pleochromocytoma - catecholamine secreting tumour grows from chromaffin cells in the adrenal gland.
Thyrotoxicosis - increased sensitivity to catecholamines by increasing beta dernergic receptor expression
Diabetic nephropathy - risk of endothelial cell dysfunction, atherosclerosis, damage to glomerulus, decrease eGFR
What is the use of thiazide diuretics to treat hypertension?
Examples: bendroflumethiazide
Naming stem:
Pharmacology: distal convoluted tubule, secreted in renal tubule in the PCT.
Blocks the Na Cl cotransporter on the apical membrane of the DCT, hence decreases activity of Na+ K+ Pump,
Physiology: Increase water and sodium ion excretion
Short term - decreased BV + CO
Long term - decrease Na+ in smooth muscle cells, decrease sensitivity to vasoporessorrs, decrease peripheral vascular resistance
Therefore decreases short term and long term blood pressure.
What is the peripheral pharmacology of cocaine?
Class: local anaesthetic and sympathomimetic
Chemistry: small molecule, amphipathic (so can cross the placenta)
Pharmacology:
As LA - reversible inhibitor of VGNa+C, the highest affinity for inactivated state
As sympathomimetic - inhibits sodium dependents noradrenaline/dopamine/serotonin transporters
Physiology:
Increase monoamines including noradrenaline in the synaptic cleft, enhances and prolonds sympathetic effects
Leads to increased activation at alpha and beta adrenergic receptors - increase HR/contractility - increase CO/ABP/TPR -includes coronary vasoconstriction so risk of MI.
What are some common signs and symptoms of cocaine use?
Excitability
Dilated pupils
Runny nose
Rapid heart rate
Evlated BP
Excessive sweating
Risky behaviour
Burst of energy
Mental health decline - anxiety, delusion, violent, paranoia, hallucination, suicidal thoguhts
What clinical signs are looked for in a suspected cocaine use case?
Tachycardia (may have palpitations/arrhythmias)
Raised blood pressure
Excessive sweating
Chest pain/difficulty bleeding
Dilated pupils
Tremors
Psychological changes: anxiety, delirium and paranoia.
What are some adverse effects of cocaine use?
Anxiety, restlessness and excitement
Tonic clonic seizures
CNS depression - respiratory failure
Cardiac adverse events - tachycardia, hypertension, cerebral or coronary artery stroke/MI
Hyperreflexivia
Mydriasis
How do sedatives reduce agitation?
Mainly prescribe: benzodiazepines as a sedative after cocaine abuse
Chemsitry:
Pharmacology:at in CNS, allosteric regulator at GABA-a receptors to facilitate the binding of GABA to GABA -A recetors, chloride ion influx resulting in hyperpolarisation of the cells
Physiology: Decreases ability of neuron to reach an action potential causing sedation and anxiolysis.
Clinical: Anxiety, epilepsy, stimulant drug overdose
What are the different stages of hypertension by clinical and ABPM hypertension reading?
Stage 1 - Above 140/90 clinical or above 135/85 ABPM
Stage 2 - Above 160/100 clinical or above above 150/95 ABPM
Stage 3 - Above 180 systolic or 120 diastolic
Isolated systolic - above 160
Accelerated/malignant HT - rapid and severe increase in BP to above 180/120
**When might a hypertension patient require referal to a specialist?
If under 40yrs old and suspect secondary cause of hypertension
If severe blood pressure stage 3 (180/120 or higher), suspect organ damage.
What causes of secondary hypertension are amenable to surgery?
Cushing syndrome -Pituitary tumour -Suprarenal hyperplasia or tumour - increased cortisol production
Primary hyperaldosteronism due to suprarenal cortical tumour
Pheochromocytoma - tumour in adrenal gland inc catecholamines.
Coarctation of the aorta - birth defect where some of the aorta is narrower - upper extremity hypertension (pressure build up behind narrowing, reduced blood flow to lower extremities activates RAAS, left ventricular hypertrophy)
Renal parenchymal compression - perinephric bleed etc, ischemia/reduced bf to kidney
Unilater pyelonephritis or polycystic kidney -
Give an overview of the pathogenesis of hypertension.
Main underlying equation:
BP = CO * TRP
Any factors that increase CO or TPR will increase BP
The main factors driving CO are thought to be Na+/H2) retention, intravascular volume, preload, SV (influenced by HR and contractility)
Define hypertension
Persistent elevation of BP in systemic arterial circulation
140/90 or above.
Based on at least two readings on separate occasions.
What are the key ideas to mention in hypertension pathophysiology?
Reduced renal sodium excretion - increased BV
Increased vascular resistance
Genetic and environmental factors
BP = CO * TPR
What are some of the consequences of hypertension on the blood vessels?
Hyperplastic arteriosclerosis
Hyaline arteriosclerosis
Cerebrovascular haemorrhage
Aortic dissection
How does hypertension cause the formation of hyperplastic arteriosclerosis?
‘onion skinning’
Is an adpative response to severe malignant hypertension
Proliferation of smooth muscle cells and reduplication of basement membrane and associated ECM due to injured endothelium producing growth factors
How does hypertension increase risk of aortic dissection?
Tear in intima and media
Allows blood to accumulate under tunica adventitia
Risk of rupture and hemorrhage
How does hypertension increase the risk of hyaline arteriosclerosis?
Primary hypertension
Deposistion of acellular hyaline material
Endothelial injury causes platelet deposition, and increased blood vessel permeability and growth factor release - results in smooth muscle cell and ECM proliferation, thickens the tunica media and intima
How does hypertension increase the risk of cerebrovascular hemorrhage?
Hypertension - breaks the elastic lamine, degenerates the tunica media, rupture thin arteires in the the brain and can cause microaneurysms that then rupture
Resulting in stroke.
What are some modifiable risk factors for hypertension?
Smoking
Alcohol
Exercise
Diet
Stress
What are the reasons underpinning the modifiable risk factors of hypertension?
Diet - sodium (water retention) and high saturated fat (atherosclerosis narrowing blood vessels)
Stress - emotional state can activate SNS
Exercise - cardiovascular training can lower BP, thought to decrease sympathetic tone, increase arterial lumen diameter and improve endothelial function
Alcohol - cause an adrenaline rush by increasing Sympathetic tone, impaired baroreceptor reflex, increase cortisol via ACTH,
Smoking - nicotine stimulates release of epinephrine and norepinephrine. damages blood vessel walls inc risk of arteriosclerosis and atherosclerosis.
What are some non-modifiable risk factors for hypertension?
Age - risk increases as age increase, due to loss of elasticity, endothelin production increases and NO production decreases, thickening vascular walls
Ethnicity - African-Caribbean and South Asian descent are at increased risk of high ABP - traditional foods high in salt,
Family history - shared genetic or lifestyle factors.
What is used for a risk assessment in a patient diagnoses with hypertension?
QRISK3
Computer algorithm
Answer questions including: age, ethnicity, sex, social history (smoking, alcohol), health conditions (A.fib, CKD, rheumatoid, migraines etc)
BMI, cholesterol, BP
Gives a score to indicate risk of adverse cardiovascular event in the next ten years
Can be filled out online in GP practise with the patient present.
What do the QRISK scores mean?
Low risk = less than 10%
Moderate risk = less than 20%
High risk = more than 20%
What investigations should be carried out to assess risk of complications in a person diagnosed with hypertension?
Fundoscopy exam
U&Es, urine disptick - kideny function
Blood glucose - risk of T2D
Serum lipids - atherosclerosis
ECG - for left ventricular hypertrophy or ischemia.
What is the presentation of untreated end stage organ damage due to hypertension?
Causes fibrinoid necrosis in bv supplying the organs.
Kidenys - hematuria, proteinuria, progressive kideny disease
Brain - cerebral oedema, haemorrhage
Retina* - see other card
CVS - acute heart failure and aortic dissection.
What is the health belief model?
