1. increased systemic vascular resistence
1.1. cardinal features of HF
1.1.1. due to
1.1.1.1. vc dt
1.1.1.1.1. neuroendocrine activation
1.1.1.1.2. NE-Ang II-endotheline-vasopressin
1.1.1.1.3. decrease response to NO dt O2 free radicals
1.1.1.1.4. Na/Ca exchange
1.1.1.2. anatomical alteration
1.1.1.2.1. thickened capillary membrane
1.1.1.2.2. vascular remodling
1.1.1.2.3. sm hyperplesia & proliferation
1.1.1.2.4. microvasular infarction
2. reduced SK.M mass dt abnormal metabolism
2.1. defect Ryanodin receptor dt hyperphosphorylation
2.1.1. decrease SK.M contraction
2.1.2. decrease excitation contraction coupling
2.2. decrease mitochondrial content
2.3. frequent apoptosis
2.4. exercise capacity & EF are not correlated so
2.4.1. LCOP is not the dominant reason for excersice intolerance
2.5. VC & redistribution of bl flowt
2.5.1. local autoregulatory VD in brain & heart
2.5.2. so decrease function of SK.M - kidney - splanchenic region
2.5.3. vasodilators correct this abnormality
3. renal responce
3.1. in HF
3.1.1. increase Na & H2O 5-40%
3.1.2. decrease K 5-20%
3.1.3. decrease Mg & increase urea
3.2. lcop --> decrease renal blood flow
3.2.1. (+) sympathetic
3.2.2. (+) RAAAS
3.2.3. (+)renal PG
3.2.4. augment vascular tone of efferent arteriol
3.2.4.1. maintain GF
3.2.4.2. filteration fraction (=GFR/renal bl. flow)
3.2.4.3. increase filteration fraction
3.2.4.3.1. increase oncotic pr + decrease hydrostatic pr of bl passing from glomeruli to peritubular cap
3.2.4.3.2. decrease Na delivery to distal tubule
3.3. shift to medullary nephron in HF
3.4. increase ANG. III + INCREASE NE
3.4.1. increase Na reabsorbtion from proximal
3.5. increase aldosteron
3.5.1. Na reabsorption from distal tubules + K & H excretion
3.5.1.1. alkalkalosis
3.5.1.2. diuretic decrease Na delivery to DT -> loss K in urin= kaluresis
3.5.1.2.1. prolonged diuretic TTT--> decrease Mg
3.6. increase vassopressin
3.6.1. H2O retension from collecting duct
3.6.1.1. dilutional hyponatremia
3.7. urea moves following water
3.7.1. more urea uptake > creat 10:1
4. increased sympathetic changes
4.1. cardiac
4.1.1. abnormal B receptors
4.1.1.1. numbers
4.1.1.2. function
4.1.2. myocyte: -
4.1.2.1. hypertrophy
4.1.2.2. fibrosis
4.1.2.3. necrosis
4.1.2.4. apoptosis
4.1.3. contraction:-
4.1.3.1. impaired
4.1.3.2. incoordinated
4.1.4. arrhthmia
4.1.5. release reactive O species
4.1.6. NE:
4.1.6.1. depressed concentratio
4.1.6.2. depressed uptake
4.2. peripheral vascular sm
4.2.1. VC
4.2.2. HYPERTROPHY
4.3. renal
4.3.1. RAAS activation
4.3.2. decrease response to naturitic peptide
4.3.3. Na tubular absorobion
5. RAAS activation
5.1. renin release (+) by:..
5.1.1. decrese renal bl flow
5.1.2. increase sympathetic
5.1.3. hyponatremia
5.2. renin -> Angiotensin II ->effects:
5.2.1. cardiac effects
5.2.1.1. +ve inotropic atrial muscles->arrythmia
5.2.1.2. hypertrophy
5.2.1.3. diastolic dysfunction
5.2.1.4. subendicardial ischemia & necosis
5.2.1.5. necrosis & remodling
5.2.2. peripheral vascular effects
5.2.2.1. increase glomerular efferent constriction-->VC-->redistribution of regional bl flow
5.2.3. aldosterone & vassopressin
5.2.3.1. potent myocardial & vascular fibrosis
5.2.3.2. by
5.2.3.2.1. direct effect on collagen turnover & composition
5.2.3.2.2. induces NADPH oxidase(source of superoxide anion) ->oxidative stress& inflammation
5.3. tissue renin-angiotensin
5.3.1. activated in compensated HF
5.3.1.1. when circulating RAAS activity is normal
5.3.1.2. also by chymase pathway (independent of ACE pathway
5.4. counter regulatory pathway in RAAS
5.4.1. angiotensin 1-7 & -1 via transmembrane ACE2
5.4.1.1. direct regulatory feedback
6. cytokine activation
6.1. increase inflammatory cytokines:e.g:
6.1.1. interlukines-TNF alpha-interferon-adhesion molecules
6.1.2. source: failing heart
6.1.3. effects
6.1.3.1. cardiac
6.1.3.1.1. apoptosis
6.1.3.1.2. impaired contraction
6.1.3.1.3. pulmonary & peripheral edema
6.1.3.1.4. O2 free radicals
6.1.3.2. systemic
6.1.3.2.1. cachexia
6.1.3.2.2. metabolic & immune dysfunction
7. other hormonal changes
7.1. increase arginine vasopressin
7.2. ANP - BNP
7.3. endotheline -1
7.3.1. myocardial fibrosis
7.3.2. Na retension
7.3.3. contribute to pulmonary hypertension