Hypertension Flashcards
Normal BP
HT BP
Malignant/Accelerated HT BP
120/80
140/90
200/120
1 Renal and 1 Aortic cause of secondary HT
Renal artery stenosis
Aortic Coarctation
Vessel effects of 2 HTs
Atherosclerosis
Arteriolosclerosis
- Benign HT: Hyaline AS - deposition of pink hyaline materials in vessel walls - plasma protein + smooth muscle remodeling; plasma protein leakage from injured endothelial tissues;
- Malignant HT: Hyperplastic AS - smooth muscle proliferation and elastic fiber deposition - fibrinoid material, fibrinoid necrosis; concentric thickening; concentric proliferation of smooth muscle cells
Fibrinoid necrosis is a specific pattern of irreversible, uncontrolled cell death that occurs when antigen-antibody complexes are deposited in the walls of blood vessels along with fibrin.
Also LVH lol
Pathology effects on Kidney, Brain
Nephrosclerosis
Cerebral hemorrage, thrombosis, HT encephalopathy
- if ischemia - liquefactive necrosis
- HT - Hemorrhage
- – Charcot Bouchard Aneurysms in small blood vessels in Basal Ganglia
- – Lacunar Infracts - ischemic stroke
Mechanisms when BP drops
Carotid Sinus, Aortic Sinus baroreceptors
- signal to CNS
- Stimulate sympathetic outflow
- alpha 1 - vasoconstriction of peripheral blood vessel
- beta 1 - CVS increase HR, contractility
Renal Blood flow decreases
- GFR drops, JGA senses, secretes renin
- RAAS released, Aldosterone released, Vasopressin released, Efferent renal artery constricts, GFR increases
- Peripheral Vasoconstriction, Salt, Water retention, CO, increases
- BP rises
Minoxidil and MLCK pathway
Potassium Channel opens - Potassium Efflux
- potassium efflux leads to hyperpolarization of cell - preventing action potential to open Ca Channel
Voltage gated Ca Channel opens - Ca Influx
Ca binds Calmodulin
Ca-Calmodulin activates MLCK
Activated MLCK phosphorylates Myosin LC;
Take this for smooth muscle only, not Cardiac (from google)
beta 2 activation and MLCK phosphorylation
beta 2 - GPCR - vasodilation + lung bronchodilation
AC - increase cAMP
cAMP phosphorylates MLCK - inactivation by PKA
- Vasodilation
NO and MLC pathway and Drugs
- which drug to look out for
NO - vasodilator
Guanylyl Cyclase - GTP to cGMP
- cGMP dephosphorylates MLC
- Vasodilation
Glyceryl Trinitrate Sodium Nitroprusside (IV)
- sildenafil - Viagra; Vasodilator too;
Potassium Channel opener
Name
MOA
AE
Minoxidil
- opens K+ channel - hyperpolarization
- less Ca, less, Ca-Calmodulin, MLCK inactivation, MLC weak
- dilating arterioles [NOT @ HEART] antihypertensive vasodilator; bought over the counter for hair loss Topically;
AE:
BP drops - reflex sympathetic + sodium + fluid;
ACE Inhibitors
Pathway, functions of ACE
Name
AE
Contra-I
ACE
ANG - ANGI by Renin
ANGI - ANGII by ACE
ACE breaks down Bradykinin - a vasodilator
- BK - releases NO, PG
Captopril, suffix pril
Note: no reflex sympathetic from BP drop as ACEI resets pressure sensitivity - hence no need beta blockers
AE:
- Hyperkalaemia (aldosterone block)
- dry cough from BK
- acute renal damage [note triple whammy; ANGII function in maintaining GFR]
Contra-I
- pregnancy - fetal renal damage
Kidney Targeting Drugs
- Names and Comparison
ACEI - ‘prils’
- Captopril
ARB
- Losartan - sartan
- less dry cough, BK continue breakdown by ACE
Contra-I for both
- pregnancy - fetal renal damage
ACEI AEs pathologies
Low BP first, Low GFR then RAAS activated - ANGII increases GFR by increase efferent vasoconstriction, then water, salt retention.
Patients w ACEI (prils) usually have a modest reduction in GFR cos less ANGII action.
In patients w Kidney diseases, heart failure, renal stenosis, GFR lowering can be severe hence need check - monitor RENAL FUNCTION
Persistent dry cough - increased BK levels
Whats Minoxidil
Potassium Channel Opener
Whats Captopril
ACEI
Whats Losartan
ARB
