pathology of hypertension

1. HTN / 1
Hypertension ( Must Know )
Hypertension ( HTN ):
Sustained elevated blood pressurewith reference to normal.
Normal blood pressure:-<130 mm Hg < 85
● Systolic < 130 mmHg.
● Diastolic < 85 mm Hg.
● Averagenormal level: - 120 / 80 mm Hg.
● High normal level :- 130 - 139 mm Hg
85 - 89
● Sustained systolic pressure equal to or more than 140 mm Hg and diastolic
pressureequalto or more than 90 mm Hg constitutes hypertension.
Accelerated or malignant HTN.
The complete picture of malignant HTN includes:
• Severe HTN, Diastolic pressure >120 mm Hg.
• Renal failure.
• Retinal hemorrhages and exudates with or without papilledema.
• Malignant HTN may develop in a previously normotensiveindividual
but usually it is super-imposed on preexisting essential or secondary
HTN.
• HTN is of two types.
1. Primary / Essential HTN : 90 – 95 % cases. [ Idiopatic ]
2. Secondary HTH : 5 – 10 % cases.
• Most cases of secondary hypertension aredue to renal diseases.
Causes of secondary hypertension:
Renal disorders.
– Acute glomerulo nephritis.
– Chronic renal diseases.
– Polycystic diseaseof the kidney.

2. HTN / 2
– Renal artery stenosis.
– Renal vasculitis.
– Renin producing tumor.
Endocrinedisorders.
Adreno cortical Hyper function.
* Cushing syndrome
* Primary aldosteronism
* Congenital adrenal hyperplasia
Exogenous hormones.
* ↑ gluco-corticoid administration.
* Estrogen including oral C/C pills.
Pheochromocytoma.
Acromegaly
Hypothyroidism.
Hyperthyroidism.
Cardio vasculardisorders.
• Coarctation of aorta
• Poly arteritis nodosa
• ↑ed cardiac output
Neurologic disorders.
• Psychogenic
• ↑ed I /C pressure
• Acute stress including surgery.
• Sleep apnea.
Incidenceof HTN increases with age.
Itis more common in black people [ 2 : 1 ]and black aremore vulnerable to its
complications.

3. HTN / 3
Hypertension is compatible with long life becauseof adaptation power of
myocardialfibers.
In mostpatients HTN remains at a moderate level and runs a long course,
spanning over years to decades unless MI or CVA supervenes.
Only about 5% of hypertensiveindividuals develop a rapidly rising blood
pressurewhich, if untreated, leads to death within 1-2 years.
Regulationof normal blood pressure.
Normal arterial pressuredepends on two hemodynamic variables i.e, Cardiac
output and total peripheralresistance.
Cardiac output largely depends on blood volume which is greatly dependent on
boy sodium [Na+
].
So Na+
homeostasis is central to blood pressureregulation.
Peripheral resistance is determined at the level of arterioles which depends on its
lumen size.
The lumen sizeitself is dependent on its wall thickness and the effects of neural
and hormonalinfluence that either dilate it or constrictit.
Normal vascular tone depends on the balance between vasoconstrictor and
vasodilator influences.

4. HTN / 4
Pathogenesis of HTN.
Note: [ Better toknow from now onwards ]
Arterial HTN develops when changes occur that alter the relationship between
blood volume and peripheral resistance.
The pathogenesis of secondary HTNis well understood.
In renal artery stenosis →
↓ GRF → ↓ pressurein afferent arteriole of glomerulus → ↑ Renin secretion
by Juxta-glomerular cells.
Renin converts Angiotensionogen to → Ang – I.
Ang – I is converted to Ang - II by ACE.
Ang-II causes vasoconstriction and increases peripheralresistanceand thus HTN.
Moreover, Ang-II also ↑es Aldosteron secretion and ↑es distal tubular
reabsorption of Na+
and thus of water so HTN.
In caseof pheochromocytoma, the catecholamine causes vascontriction and thus
induces HTN.
The pathogenesis of essential HTN is quite complex and multifactorial.
Itoccurs as a result of interaction between genetic and environmental factors.
Genetic factors.
Essential HTN is a multiple gene defect but single gene defect also rarely causes
HTN.
Genetic defects of enzymes responsiblefor aldosteron metabolism leads to an
Adaptive ↑in secretion of aldosteron.
↑ aldosteron causes salt retention and subsequentwater retention →↑ blood
volume and HTN.
Deficient enzymes responsiblefor defective aldosteron metabolism include:-
• Aldosteron synthetase.
• 11-Bhydroxylase.
• 17α-hydroxylase.

5. HTN / 5
Liddle syndrome:-
Mutation in single gene of epithelial Na+
channel protein → ↑es distal tubular
Na+
reabsorption induced by aldosteron.
Environmental factors.
Environmental factors causeexpression of genes responsiblefor ↑ blood
pressure.
↓ incidence of HTN in Chinese living in china as compared to people of Chinese
descent living in USA.
Stress, obesity, smoking, physicalinactivity, heavy ingestion of salt and estrogen
all contribute to the actiology of HTN.
Mechanism:-
Two inter related pathways areresponsiblefor a primary defects in essential HTN.
Renal retentionof excess Na+
:
Defects in renal Na+
homeostasis arethe primary causeof HTN.
The genetic defects result in ↓ renal Na+
excretion in the presenceof normal
arterial pressureas an initial event.
↓Na+
excretion leads to ↑ in fluid volume and ↑ cardiac out.
As a resultof ↑ cardiac output, peripheral vasoconstriction occurs dueto auto
regulation to prevent over perfusion of tissues.
The ↑ peripheralresistanceas a result of auto- regulation, however leads to ↑
blood pressure.
At this higher level of BP, enough Na+
can now be excreted by the kidney to equal
intake and prevent fluid retention.
In this way altered but steady state of Na+
excretion is achieved (resetting of
pressurenatriuresis) butal the expense of stable increase in blood pressure.
Vaso constrictionandvascular hypertrophy.
This concept considers ↑peripheral resistanceas primary causeof essential
hypertension.
The ↑ed peripheralresistance is either due to functionalvasoconstriction or due
to stimuli responsiblefor structuralchanges in the vesselwall.
The structuralchanges include hypertrophy, remodeling and hyperplasia of SM
cells leading to thickened wall and narrowed lumen or both of these effects.

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Vasoconstrictiveinfluences may be:
• Neurogenic
• ↑ release of vasocontrictiveagents like rennin, catecholamine,
endothelin.
• ↑ed sensitivity of SM cell to constricting agents.
This ↑ed sensitivity is caused by a primary genetic defect in transportof Na+
and
Ca+ and contraction of smooth muscles.
If such vasconstricting influences persistchronically or repeatedly, these may
themselves cause thickening of walls of resistancevessels.
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