Exam 3 patho

Main components of Blood Vessels

endothelial cells, smooth muscle, extracellular matrix- elastin, collagen, glycosaminoglycans

Categories of blood vessels based on size & structural function 

Arteries, Arterioles, capillaries, venules, veins

Role of blood vessels

transport blood to tissues, regulate blood flow to tissues, control BP and secrete a variety of chemicals

Concentric layers of blood vessels

intima, media, adventitia

(most inner, middle, outer)

make up the tunica

play a role in blood pressure control 

Arteries

convey blood from heart to capillaries moves away from the heart

-high blood pressure here

-thicker tunica media, narrower lumen than veins

-has more elastic and collagen fibers (spring back to shape)

-more resistant to change in blood pressure

Elastic Artery

Aorta- conduct blood from heart to muscle arteries -large proportion of elastic fibers allowing stretch and recoil 

Muscular Artery

medium-sized blood vessels that distribute blood from the elastic arteries to the body's organs and tissues (specific body regions)

include most named arteries (brachial, coronary

vasodilation and constriction

Arteriole

a small branch of an artery leading into capillaries.

smallests of the arteries

sm is always somewhat constricted (vasomotor tone)

regulate systematic blood pressure and flow 

Veins

transport blood from capillaries to heart

have thicker tunica externa and larger lumen than arteries

have less collagen and elastic fibers

walls collapse if no blood in vessels

Venules

smallest vein companion vessels with arterioles 

smallest venules are postcapillary venules merge to form veins 

small/medium veins

companion vessels with muscular arteries

Large veins

travel with elastic arteries

-numerous valves to prevent backflow (made of tunica intima)

Capillary

small vessels connecting arterioles to venules

small diameter optimal for exchange between blood and tissue fluid

Blood vessel disorders

Arterial disorders

venous disorders

Arterial disorders

hypertension

atherosclerosis

aneurysm and dissection

Vasculitis

Vasculitis blood vessel, hyperactivity

Venous disorders 

varicose veins

normal blood pressure

120/80

systolic/diastolic

Hypertension

American college 130/80 mmHg

European 140/90 mmHg

Hypertension definition

persistently elevated arterial blood pressure greater or equal to 13/90 resulting from genetic and environmental factors

affects mostly small muscular arteries and arterioles

accelerates atherogenesis (increase plaque in the lumen of vessel) and causes degenerative changes in vessel walls (lg, med)

boarderline elevated htn

120-130 mmHg systolic

Types of HTN

Primary Htn (90-95% common)

Secondary HTN 

Primary HTN

Essential or idiopathic hypertension

90 to 95% of individuals with hypertension

Caused by an increase in either both cardiac output, or total pressure resistance

CO=Heart rate(stroke volume-force) 

This type of hypertension is multifactorial induced by genetic and environmental factors

primary htn mechanisms

renal mechanism, vascular, genetic, environmental

Renal mechanisms

insufficient NA+ excretion leads to increase in fluid volume leading to an increase in CO

“resetting of pressure natriuresis”

-in this scenario, the NA+ stays in the blood, which causes water to follow, causing h2o to stay in the system causing an increase in blood pressure and increase in CO

Vascular mechanisms

vasoconstriction + structural changes leads to increase in total pressure resistance (lumen size of vessel)

Genetic factors

single gene disorder leads to rare forms of hypertension

more than 500 genetic loci (susceptible genes)

Environmental factors

stress, obesity, smoking, physical, inactivity, heavy salt consumption

Treatment for hypertension

lifestyle changes

drug treatments

lifestyle changes 

Exercise

Diet (decrease salt intake and increase weight loss)

eliminate stress

stop smoking

drug treatments

depend on many factors: dilate vessels and get rid of fluid

diuretics (pee out)

b1 blockers (decreases CO)

ACE inhibitors

calcium channel blockers

a1 blockers (prevents vasocontraction)

Secondary Hypertension 

5-10% of individuals present 

disease→ HTN

altered hemodynamic function due to primary disease condition 

underlying conditions: renal, endocrine, cardiovascular, neurological diseases; example, renal artery stenosis, or other identifiable causes

Mechanisms of secondary hypertension

renovascular HTN

Primary hyperaldosteronism

single gene disorders

Renovascular HTN

RAS: decrease glomerular flow and pressure in afferent arteriole causes increase of renin secretion causes increase blood volume and vascular tone

Decrease blood flow froma disease like astenosis causes…

renin secreted @ kidney

activation of angiotensinogen @liver → Angiotensin I

Angiotensinogen I is activated by ACE @ lungs→ activation of angiotensinogen II

→ increase in aldosterone which causes an increase in Na+ reabsorption which causes increase water and increased blood volume

Primary hyperaldosteronism (part of secondary htn)

idiopathic or aldosterone secreting adenomas

increase in aldosterone which causes NA+ reabsorption-aldosterone comes from the adrenal gland .

Single gene disorders

gene defects affecting enzymes involved in aldosterone metabolism causing an increase in aldosterone which leads to an increase in aldosterone in the vessels

-mutations affecting proteins that influence sodium reabsorption, for example if the body can’t regulate NA+ channels causing an increase in reabsorption

Underlying diseases that lead to secondary HTN

renal, endocrine, cardiovascular, neurologic

Atherosclerosis

plaque build up

-progressive disease that affects the arteries

mainly elastic and muscular arteries

characterized by accumulation of plaque leading to narrowing vessel lumen

What is the problem with plaque?

atherosclerosis is characterized by a buildup of plaque so this causes narrowing lumen of blood vessels.

risk factors can lead to intimal lesions called atheromas or atherosclerotic plaques that protrude into the vessel lumen

what happens?

-obstructing flow

rupture→ thrombosis 

thickened wall→ischemic injury and weakened media wall leading to aneurysm formation 

Risk factors for atherosclerosis

Acquired factors, inherited factors, gender- and age associated factors

Acquired factors

hypertension, cigarette smoking, hyperlipidemia (low density, lipoprotein, or LDL) parentheses, diabetes, inflammation

Inherited factors 

Family history, and genetic abnormalities

Gender and age factors

increasing age and male gender

Atherosclerotic plaques consists of

fibrous cap and necrotic center

tunica intima is broken

fibrous cap

smooth muscle cell, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycan, and neovascularization 

Necrotic center

cell debris, cholesterol, crystals, foam cells, calcium

foam cells

macrophage that have endocytosed lipid cells

Pathophysiology of atherosclerosis

endothelial injury→ chronic inflammatory and healing response 

lesion progression involves LDLs, macrophages and T cells interacting with endothelial and smooth muscle cells of the arterial wall

Simple terms patho of Atherosclerosis

chronic condition (endothelial injury) → endothelial dysfunction→macrophage activation→SMC/ Macrophage engulf lipid→deposition →plaque thickens

Complications of atherosclerosis

MI -heart attack

cerebral infarction (stroke)

aortic aneurysm (wall weakens and bulges)

peripheral vascular disease- narrowing periphery and lymph vessels

Mesenteric occlusion

chronic ischemic heart disease

sudden cardiac death

ischemic encephalopathy (brain tissue)

Vasculitis

information of vessel, walls, it affects vessels of certain caliber and location,

frequently associated with fever, myalgias, arthralgias, organ dysfunction

Common mechanisms of vasculitis

immune mediated inflammation-complex deposition

Direct invasion of vascular walls by infectious pathogens

Vasculitis diseases 

Granulomatous disease (giant cell arteritis)

Kawasaki disease

Churg-Strauss syndrome 

Buerger disease

Giant cell arteritis - Granulomatous disease

large vessel vasculitis

common in r temporal region

must be treated with steroids right away

facial pain/ headache, ocular symptoms

• Aorta +

• affects temporal, vertebral and ophthalmic arteries

• greater than 40 yrs with or without polymyalgia rheumatica

Kawasaki disease

medium vessel vasculitis in the arteries

anti-endothelial cell antibodies in a young child

symptoms

Fever for five days, cervical lymph nodes, greater than 1.5 cm, rash, bilateral conjunctivitis, coronary artery aneurysms(long term problem), swelling of palms and soles of feet, mucositis of the mouth

Churg-Strauss syndrome

small vessel vasculitis

presence of asthma and allergies, increased levels of eosinophils in blood vessels.

eosinophilia, asthma, and granulomas

skin and kidney problems, immune complex mediated, presence of purpora

• small arteries

• eosiniphils req.

• asthma and atopy (genetic predisposition to developing allergic conditions, such as asthma, eczema)

Buerger disease

• thromboangiitis obliterans

• thrombosis req

• young male smoker

Specifics of thromboangiitis obliterans

Buerger’s Disease

vasculitis of the small and medium sized arteries in the upper and lower extremities

-this disease is characterized by lack of perfusion/oxygenation of the tissue 

tibial and radial arteries 

inflammation leads to thrombosis, fibrosis and scar tissue formation 

-can affect the nerves as well, strongly associated with cigarette smoking (95% of cases)

Symptoms: pain at rest, claudicatio (only pain when they are doing something) , venus inflammation 

Complications: ulceration, gangrene, amputation 

Treatment: stop smoking at earlier ages 

Blood vessel hyperactivity

vasospasm and contraction

Raynaud Phenomenon

bv hyperactivity

exaggerated vasoconstriction of arteries and arterioles in response to too cold or emotional

Extremities: fingers, toes, earlobes, nose or lips

Mechanism vasoconstriction→ restricted blood flow→ pallor (pale white)and cyanosis (purple /blue, lack oxygen 

Primary raynaud phenomenon

young womenonly disease affecting pt

symmetrically affecting the extremities (both limbs)

triggered by intrinsic hyperactivity of the smooth muscle cells which contract and cause narrowing of the BV

secondary raynaud phenomenon

caused by another disease such as SLE, scleroderma, buerger disease, or atherosclerosis

asymmetric involvement of extremities that progressively worsens over time

Varicose veins

abnormally dialated veins, prolonged increased intraluminal pressure and by loss of support of the vessel wall \

occurs in superficial veins of the upper and lower leg

ex. the great saphenous vein can become so dilated that it can no longer do its job

causes, s/s, tx. of varicose veins 

increase in localized venus pressure- prolonged standing or pregnancy/obesity

s/s- aching, swelling→ stasis dermatitis, ulceration→ poor wound healing

tx. stockings or surgery 

what is stasis dermatitis: pooling of blood in the veins  

varicose veins at the esophageal varices

varicose vein that develops in the lining of the esophagus. Their formation is primarily driven by portal hypertension, an increase in blood pressure within the portal venous system

This elevated pressure causes blood to bypass the liver through collateral veins, leading to their dilation and tortuosity, particularly in the lower esophagus

The veins connecting the portal system to the systemic circulation in the lower esophagus are particularly susceptible to this increased pressure. As blood is shunted through these veins, they become engorged, dilated, and tortuous, forming esophageal varices. The increased intraluminal pressure causes these veins to bulge into the esophageal lumen

often if the liver can’t function , blood moves backwards in systemic circulation causing varices that can cause the esophagus to easily tear 

hemorrhoids 

occur in the anal and rectal area. Their development is fundamentally linked to the same mechanisms that cause varicose veins elsewhere in the body: prolonged, increased intraluminal pressure within the veins and a loss of support in the vessel walls. This leads to the abnormal dilation and tortuosity characteristic of varicose veins

• Increased Localized Venous Pressure: Elevated pressure within the veins of the anal canal and rectum is a key factor. This pressure can be exacerbated by activities that strain the abdominal and pelvic regions

• Prolonged Standing: Similar to varicose veins in the legs, prolonged standing can increase pressure in the venous system, including the pelvic veins, which contributes to the development of hemorrhoids

• Pregnancy/Obesity: These conditions significantly increase intra-abdominal pressure, which in turn elevates venous pressure in the lower body and pelvis, predisposing individuals to both lower extremity varicose veins and hemorrhoids

Cardiovascular system

heart, blood vessels, blood

Circuits of the cardiovascular system 

heart pumps blood via the pulmonary and systematic circuits 

Pulmonary circuit 

blood moves from the pulmonary artery at the right side of the heart to the lungs, where the blood becomes oxygenated, then the blood moves through the pulmonary veins into the left side of the heart (atrum to ventricle) 

Systematic circut

blood moves from the left ventricle into the aorta then blood is perfused around the body and blood re-enters the heart via the vena cava and moves into the right atrium

Six mechanisms that lead to a broken heart

failure of the pump

obstruction to flow

regurgitant flow

shunted flow

disorder of cardiac conduction

rupture of the heart or major vessels

Congestive heart failure 

inability to effectively pump blood to meet the metabolic demands of the tissues 

or req. elevated filling pressures 

Etiologies that lead to CHF

ischemic heart dz (coronary vessels are blocked)

Hypertension

valvular heart disease

arrhythmias

congenital defects

cardiomyopathy (thickening of the heart muscle, deposition of proteins that prevent normal function

Cardiac hypertrophy

increase in size of cells of the heart

causes progression to CHF

Patho of cardiac hypertrophy 

sustained increase in mechanical work (pressure/volume overload) leads to cell hypertrophy

the heart tries to maintain CO so therefor it has to work harder 

increase in DNA ploidy- increase in chromosome sets in the heart cells 

Pattern of hypertrophy

1. increase in wall thickness and mass→ sarcomeres parallell→ pressure overload

2. increase in mass→sarcomeres assembled in series→ volume overload

Patho of cardiac hypertrophy 

increase in mechanical work

changes to gene expression, HR/contractility, oxygen supply, fibrous tissue deposition 

Hemodynamic changes and circulatory problems

Brain natriuretic peptide amd ECG used to assess extent of CHF 

Hemodynamic changes and circulatory problems in CHF

decrease in CO, BP, tissue perfusion (forward failure (to body))

pooling of blood (backward failure (back to heart toward lungs))

Left sided Congestive heart failure

most often caused by IHD or HTN, aortic and mitral valvular disease or primary myocardial disease

passive congestion (blood backing up, stasis of blood in the chamber and inadequate tissue perfusion

compensation: catecholamine release (NE/E), RAAS, ADH (antidiuretic hormone)

Left sided CHF Key

Backward effect: backing uo of blood to lungs (cause shortness of breath)

increase pressure behind pump leads to pulmonary congestion 

Forward effect: low cardiac output to body (dilation of left ventricle and aorta)

organs involved: heart lungs kidney brain

Mechanism/ compensation with L CHF

Pt. 1

Myocardial dysfunction: there is a presence of a condition that prevents blood from being pumped out of the heart

-MI, IHD, HTN

As a result there is a decrease in CO and systemic BP bc blood is not being pumped out of the heart.

Baroreceptors activate and detect pressure change (located at left ventricle, aortic arch, or carotid sinus)

These receptors then signal the medulla in the brain’s to activate the sympathetic system and trigger the adrenal gland to produce catecholamines (NE/E)

These hormones cause vasoconstriction and lead to an increase in afterload, BP, and heart rate 

this causes ventricular remodeling (Hypertrophy and dilation of the ventricle-genetically large cells with impaired contractility)

PT 2.

Myocardial dysfunction: there is a presence of a condition that prevents blood from being pumped out of the heart to the kidneys 

-MI, IHD, HTN

When blood is not pumped to the kidneys, the kidneys produce renin, which triggers the RAAS pathway 

Renin activates angiotensinogen - Angiotensin I @ liver

ACE @lungs activates Angiotensin I- Angiotensin IIAngiotensin II goes to the adrenal cortex and aldosterone is produced.

Aldosterone causes an increase in NA+ reabsorbtion which leads to in increase in H2o and blood volume 

Result: increase in Blood volume (afterload), vasodilation, HTN,  heart rate

leads to ventricular remodeling 

Left sided dysfunctions

systolic

diastolic

Systolic dysfunction

inability to contract/ pump

reduced contractibility of LV→ decrease in CO and BP→ inadequate tissue perfusion

Diastolic dysfunction

inability to fill (relax)

LV abnormally stiff and can not relax during diastole

any increase in filling pressure→ pulmonary congestion

exacerbated with increase in metabolic demands

Etiology- HTN> DM, obesity, renal artery stenosis

Right sided heart failure

inability of the right side of the heart to pump blood to the lungs.

most common cause is left sided CHF, causing pulmonary congestion.

Isolated right-sided CHF can be due to a variety of lung disorders, like primary pulmonary HTN

Core pulmonale- diagnosis when RCHF is due to another condition like COPD, pleural effusion, or cancer

Right CHF flow

Backward: to systemic congestion of the body (pooling of blood at body)

Forward Low cardiac output to lungs

Organs: heart liver portal system, spleen, kidney, subcutaneous tissue, brain

often JVD is seen

Ischemic heart disease

a group of syndrome caused by lack of oxygenation, nutrients, and removal of metabolic waste

Greater than 90% are due to coronary atherosclerosis

less common causes: coronary emboli, myocardial vessel inflammation, vascular spasm (smooth muscle contraction)

Progression: begins silent→ sudden onset of symptoms

Some people may not realize they have this condition because the obstruction takes time to build up

CAD

coronary artery disease- coronary athersclerosis (vessels of the coronaries)

involves LAD, RCA, LCX

left descending, left circumflex, right coronary artery

Clinical manifestation of IHD

Angina pectoris- chest pain

myocardial infarction (heart attack)

chronic IHD with heart failure (lack of pumping)

sudden cardiac death (SCD)

Angina Pectoris

characterized by paroxysmal and recurrent attacks (occur quickly and uncontrollably) location: substernal or precordial (infront of heart) chest discomfort

Transient ischemia 

not severe enough to cause necrosis (15 seconds to 15 minutes) 

Three patterns of angina

stable (typical) angina

Prinzmetal variant angina

unstable (crescendo) angina

Stable (typical angina)

some obstruction from narrowing of coronary artery causing insufficient blood flow to the heart

stable angina often leads to unstable angina

most common caused an imbalance and coronary confusion related to demand: how much blood the heart gets vs how much it needs 

Associated with underlying CAD

Pain on exertion or increased demand, for example, pain could increase with extreme emotions or exposure to the cold

Type of pain:

Crushing or squeezing pain that radiates

Relieved by rest or vasodilators

Often described as "left sided pain “

Prinzmetal variant angina 

Has nothing to do with plaque, part of vasospasm

This is a type of episodic ischemia caused by coronary artery spasm, this comes and goes, and has nothing to do with atherosclerosis 

Unstable crescendo angina

progression from stable angina it has more long-term obstruction, often longer than 20 minutes of prolonged pain and frequency

Precipitated by less exertion or rest

Associated with plaque disruption and superimposed thrombosis (tear of vessel causes thrombosis), embolization of thrombus and or vasa spasm

Embolization of a thrombus is when the thrombus moves through circulation and gets caught causing pain

high risk of MI

NEXT STEP- MI

Myocardial Infarction

death of cardiac muscle due to prolonged ischemia

Referred to as heart attack

10% occurs in less than four-year-olds, 45% occurs in less than 65-year-old

Majority occur in the left ventricle

Risk factors MI

increasing age

Male gender

Post menopausal women-estrogen is a protective feature

Increase atherosclerotic risk factors (genetics, age, smoking, male, hypertension)

Mechanism MI

90% relates to this mechanism

Atheromatous plaque disrupted lead to hemostasis (clottong) activated, causing completely occluded vessels

Other mechanisms of MI

Vaso spasm- with/without atherosclerosis, platelet, aggregation, or drug ingestion like cocaine

Emboli-thrombus (blood clot) circulating in the blood that comes from somewhere else

Uncommon causes include vessel disorders, like vasculitis, hematologic abnormalities, amyloid deposition in walls, and vascular dissection

Patterns of infarction

myocardial, necrosis correlates with the location of the infarction

Types include transmural, infarction, and sub, endocardial infarction

Transmural infarction 

The whole vessel is obstructed

Occlusion of epicardial vessels

Necrosis involves full or nearly full thickness of ventricular wall

(across whole vessel wall)