HF with persistent HTN: ACE-I** (to prevent LVH)
Essential HTN first line symptomatic relief
Systolic CHF and MI, what drug proven for both
BB, especially carvedilol, a B1 and B2 and Alpha 1
Compensatory reactions to HF?
Activation of RAAS leads and sympathetic nervous system leads to increased afterload from excessive vasoconstriction, excess fluid retention and deleterious cardiac remodeling (from increased preload and afterload)
BNP is released by
Ventricles, in response to stretch, like during CHF, particularly systolic dysfunction that leads to stretching of atria and ventricles beyond appropriate stretch to cause maximal contraction
Often elevated in patients with CHF and so can possibly check if there is a CHF exacerbation
BNP, function? :Vasodiltation, diuresis/natriuresis, and decrease in BP thus alleviating symptoms of HF. Vasodilation via GC/cGMP; counteract endothelin, sympathetic effects and A2.
ANP/BNP on kidney?
Dilate afferent and constrict efferent while decreasing Na absorption at renal collecting tubule. Constributes to ALDOSTERONE ESCAPE mechanism. Causes vasodilation and promotes diuresis.
Recombinant form of BNP? Use?
Nesiritide. Used in patients with decompensated forms of left ventricular dysfunction leading to CHF.
Endothelin release is mediated by
Endothelin causes an increase in
Afterload via vasoconstriction.
2 triggers of ANP
HTN and hypervolemia
ANP acts on to kidney to... on adrenal gland to... and on blood vessel to...
On kidney-dilates afferent arterioles, increase GFR and urinary excretion of Na and H20; limits Na absorption and renin secretion/ ALDO ESCAPE; On Adrenal glands- Restricts aldosterone secretion leading to increase in sodium and water excretion/ ALDO ESCAPE; On Blood vessels to- relax vascular smooth muscles in arterioles and venules producing vasodilation/ cGMP. Also increases capillary permeability.
Diastolic heart failure, LVEDP? LVEDV?
Increased LVEDP from decreased ventricular compliance but normal LVEDV and stroke volume** whereas systolic HF would have increased LVEDP and increased LVEDV.
Heart failure definition
Cannot pump enough blood to meet tissue metabolic requirements or can do only from an elevated ventricular filling pressure
Golden yellow or brownish cytoplasmic granules - if they do not turn Prussian blue stain blue-black then...
Then lipofuscin, rather than hemosiderin.
Hemosiderin is made of
Macrophages having phagocytozed iron containg proteins and erythrocytes that extravasated into the alveoli from high intravascular pressures
Lipofuscin is product of
Free radical injury AND LIPID PEROXIDATION. Seen inheart and liver of aging cachectic malnourished patients.
Lipofuscin is insoluble composed of
Lipid polymers and protein-complexed phospholipids
Most common cause of pulm HTN?
Chronic obstructive pulmonary disease -> obliteration of segments of pulmonary vasculature.
Primary pulmonary HTN, young women 20-40, histopath
Progressive proliferation of endothelial cells, smooth muscle cells and intimal cells + striking medial hypertrophy of arterioles and small arteries + concentric laminar intimal fibrosis
Suden cardiac death in otherwise young person ?
Always consider WPW. Small accessory AV impulse conduction pathways anatomically separate from AV node
LV wall is 1 cm whereas RV wall is like
ISCHEMIA ATHEROSCLEROSIS CAD
Coronary steal phenomenon
When a coronary vessel is partially occluded and ischemic, coronary arterioles in that area respond to local mediators and vasodilate to direct collateral blood supplies to the ischemic area. Drugs, such as adenosine and dipyridamole, are selective vasodilators of coronary vessels. When applied to ischemic area, now arterioles in non-ischemic areas also maximally vasodilate and leading to decreased perfusion pressure in collateral vessels supplying ischemic area; blood diverted from ischemic to nonischemic areas and this can cause hypoperfusion and worsening of existing ischemia.
Renal failure + toe gangrene or livedo reticularis following invasive vascular procedure like angioplasty =
Atheroembolic renal disease. During procedure, cholesterol containing debris gets pushed elsewhere causing ischemia in corresponding organs and tissues, frequently involving kidneys.
Hyperplastic arteriolosclerosis of renal arterioles
Malignant HTN; concentric lamellar duplication of smooth muscles
Breach in the continuity of all three layers of a blood vessel (rather than a weakening of all three leading to outpouching) leading to blood leakage and hematoma formation outside the vascular wall; resulting hematoma is contained within the sac of connective tissue surrounding the original point of arterial wall rupture. Ex, post infarction myocardial ruptures contained by pericardium.
GCA leads to granulomatous inflammation of ...
Media. And fragmentation of the internal elastic lamina due to autoimmunity of elastin.
PH-HTH- Passive increase in pulmonary capillary and arterial pressure secondary to pulmonary venous congestion**, resulting endothelial damage and leakage of proteins into the interstitium will lead to increased production of ? and decreased production of ?
Increased production of endothelin/ vasoconstrictor and decreased production of NO/ vasodilator -> remodeling of pulmonary vasculature + increased smooth muscle proliferation with collagen and elastase deposition.
Remodeling more or less intense in primary Pulm HTN vs secondary Pulm HTN (secondary to passive increase in pressure)
More intense in primary pulm HTN and so less reversible.
In P HTN in setting of left heart failure, pulmonary arterial flow...
Same or decreases.
What stimulates production of endothelial NO (endothelial cells in coronary vasculature) via an intracellular increase in Ca
Endothel cell dysfunction – denudation and exposure of subendothel collagen – PLT adhesion – GF from monocytes and PLT stimulate medial smooth muscle cell migration and proliferation + increased permeability allows LDL cholesterol into intima, phagocytosed by accumulating macrophages and SMCS – foams cells – conrhic inflammatory state maintained by cytokines and GF from macrohpages and lymph - continued depositions of LDL cholesterol and new intimal SMCs – more ECM, like collagen and proteoglycans + necrosis of foam cells and release of lipid contents including toxic oxidized LDL in ECM of intima – fatty streak within the lipid laden foam cells) -> full-fledged fibrofatty atheroma*.
Core of lipid surrounded by monocytes, lymphocytes, firous cap with intermixed SMCs -> intimal thickening.
Not involved in atherosclerotic plaque and fibroma
Fibroblasts or mast cells or pericytes
Fibrous cap synthesized by
SMCs, not fibroblasts
Atherosclerosis, what is role of PLTs
Endothel dysfunction -> promotes PLT adhesion, aggregation and release of GF and cytokines, most importantly PDGF, which is also released by the dysfunctiona endothelial cells themselves and macrophages. PDGF -> migration of smooth muscle cells from media into the intma and increases smooth muscle cell proliferation. PLTs also release TGFb which is chemotactic for smooth muscle cells and induces interstitial collagen production.
B-Lymphocytes and atherosclerosis
Antibodies to oxidized LDL localize to atherosclerotic plaques and rise following acute coronary event
Vascular reaction to intimal injury?
Migration of smooth muscle cells across IEL and into the intima; followed by SMC proliferation and collagen synthesis to form a neointima. Results in reactive intimal hyperplasia.
Injured endothelial cells release growth factors that promote SMC migration and proliferation such as ...
PDGF, and can express cell adhesion molecules, VCAM that allow for adherence of monocytes and lymphocytes as well as their diapedesis into the intima. WBCs then secrete further cytokines and GFs to promote SMC migration into and proliferation in the intima, encouraging the fibrogenesis/ elaboration of collagen and ECM. If intimal injury is real severe, PLT adhesion to collagen and they then release PDGF.
In atherosclerosis, who/what is responsible for intimal thickening?
Smooth muscle cells**. Post injury, they migrate, proliferate and synthesize new connective tissue. Synth of new collagen, elastin, and proteoglycans.
Intimal thickening, smooth muscle cells or fibroblasts?
Smooth muscle cells.
Atherosclerosis, negative prognostic factors for atherosclerotic plaque?
Thin, fibrous cap; rich lipid core; active inflammation in the atheroma would decrease plaque stability and potentially promote rapid coronary occlusion via superimposed thrombosis if the plaque ruptured
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