Lecture 9 Hypertension and Diabetes

From Iusmphysiology

Revision as of 20:13, 31 January 2011 (edit) 24.15.60.132 (Talk) (→=Endothelial cells) ← Older edit		Revision as of 06:18, 9 March 2012 (edit) (undo) 192.162.19.21 (Talk) (eTzX1x I loved your blog article.Much thanks again. Fantastic.) Newer edit →
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	*continued here from [[Lecture 8 Shock]] on 01/28/11 at 9:20 AM.		*continued here from [[Lecture 8 Shock]] on 01/28/11 at 9:20 AM.
-	==Hypertension and Diabetes==	+	eTzX1x I loved your blog article.Much thanks again. Fantastic.
-		+
-	===Objectives===	+
-	*What are the systolic and diastolic arterial pressures usually used as indicators of hypertension?	+
-	*What is the labile stage of essential hypertension?  What is the primary mechanical cause of increased arterial pressure?	+
-	*How does the sustained phase of essential hypertension differ from the labile phase in terms of mechanical cause of increased arterial pressure?	+
-	*What are the general characteristics of essential hypertension in terms of the following items:	+
-	**Resistance of the majority of vascular beds	+
-	**Constrictor response to norepinephrine	+
-	**Cardiac work load	+
-	**Long term changes in arteriolar wall distensibility and smooth  muscle development	+
-	*Understand how each of the following treatments of hypertension can be effective to lower the arterial blood pressure	+
-	**Sodium restriction or diuretic loss of sodium	+
-	**Beta blockers for the heart and alpha blockers for the vessels	+
-	**Central nervous system suppression of sympathetic nervous  system activity	+
-	**Peripheral acting drugs which cause vasodilation	+
-	**Angiotensin converting enzyme inhibitors and blockade of angiotensin II receptors	+
-	**Correction of insulin resistance	+
-		+
-	===What is hypertension===	+
-	*Smoking was exchanged for eating.	+
-	*If bp gets above 140/90, we say pt is hypertensive.	+
-	**Age doesn't matter.	+
-	*90-95% of all cases of hypertension are caused by abnormal hyper-reactivity to noreepi and angiotensin II	+
-	*Risk factors:	+
-	**Agiing	+
-	***This is probably because kidney function decreases so we can't handle NaCl imbalances.	+
-	***Obesity and sedentary accelerates this process.	+
-	****80% of people over 60 are obese	+
-	**Race	+
-	***African Americans: genetics and obesity affect this	+
-	**Mexican-Americans, too.	+
-	**Menopause	+
-	***Estrogen replacement used to be the go-to therapy, but now we don't do this because estrogen increased obesity and hypertension	+
-	**Diabetes mellitus, type 1	+
-	**Insulin resistance	+
-	**Sodium intake	+
-	***BP goes down if sodium intake goes down	+
-	***Could be a problem with the H/Na pump in the kidney.	+
-	**Family history	+
-	**Stressful life	+
-	***Has lots to do with being able to handle personal and professional relationships	+
-	**Low arobic condition	+
-		+
-	====Na and hypertension====	+
-	*Impairment of sodium handling in contractile cells leading to vasoconstriction	+
-	**Na/H antiport is excessive, bringing too much Na into cell	+
-	**Low function of Na/K pump due to endogenous ouabain or similar compounds	+
-	**Both possibilities depolarize the muscle cell, increase calcium intake for removing sodium ions, and likely open voltage dependent calcium channels - the cell is hyperactive	+
-	*Ouabain blocks the Na / K pump	+
-	*Lots of hand waving in hypertension!  One of these is broken, but this is multifactoral.	+
-		+
-	===Various Mechanisms of Hypertension===	+
-	*Less than 5% of hypertension is due to these things.	+
-	*Renal tissue or vascular disease to increase renin-angiotensin-aldosterone production	+
-	**Water is retained	+
-	*Obesity (covered latter)	+
-	*Pheochromocytoma	+
-	**tumor that increases epi and ne	+
-		+
-	====B  Essential Hypertension: What Is Wrong With the Cardiovascular System====	+
-	*There is evidence that people with essential hypertension have too much cardiac output as youth.	+
-	*By the tyme they are fully int ohypertension, they have normal output witha  hypertropied heart.	+
-	*Over time the primary reason for hypersention is ?	+
-	*In the early phase is called the "early" or "labile" stage.	+
-	**They are hypertenstive when stressed.	+
-	**"White coat hypertension"	+
-	**Hence we have them follow bp at home.	+
-		+
-	*Possible outcomes	+
-	**CV system resets the setpiont pressure and regulates to maintain it.	+
-	**barroreceptros and sympahtetics must reset to meet this new point.	+
-	*Problem:	+
-	**Heart hypertrophies	+
-	**Smooth muscle cells of vessels hypertrophy	+
-		+
-	====Established phase of hypertension====	+
-	*Most who get hypertension are in the 30s / 40s.	+
-	*Unless they see a physician regularly, they may not get caught early.	+
-	*Pharma can stop it, but it will often come back worse if they stop the pharma.	+
-	*Losing weight is good because pressure will come down and will rise at a lower rate.	+
-	*Remember that all the vascular beds are involved in this disease.	+
-	*The microvasculature is in great shape in hypertension	+
-	**they heal, they vasodialte / constrict.	+
-	**Just set at a higher setpoint pressure.	+
-	*Cardiac output is ok	+
-	*Blood volume is a little higher in bp	+
-	**But this is hard to measure, really so data is a little unreliable.	+
-		+
-	====d.  Neural and Hormonal Issues====	+
-	*Sympahteics are running high to support blood flow	+
-	*Kidneys and heart are the primary targets	+
-	*Kidney	+
-	**Might cut sympathetic innvervation to help with tx.	+
-	*Heart:	+
-	**Innervation increases contractility	+
-	**Rate is fine	+
-	*Obesity:	+
-	**In general, it accentuates the sympathetic activity	+
-	**More leptin is released.	+
-	**So decreasing weight decreases leptin decreases sympathteic which is good	+
-	*Renin, angiotensin II, and aldosterone	+
-	**Blocking renin-angiotensin is very effect	+
-	**Captopril, was first, based on venom; seen from snake that bites and cuases fainting	+
-	**Acutely blocks ACE, bp drops fast	+
-	*Increased constrictor response to norepi	+
-	*Heart forced to work harder and msucle enlarges	+
-	*Arterial baroreceptors reset to  high pressure range	+
-	*Kidney absorbs more sodium from filtered fluid than in normotensive people	+
-	**If you give salt to a hypertensive person, they get rid of it faster than a healthy person.	+
-	**But na retention have to be off by much to change physiology.	+
-	*Arterioles forced to survive at high pressure	+
-	**SHR = spontaneously hypertensive rat	+
-	**Note that the high pressure of SHR is most apparent at the large arteries.	+
-	**The smooth muscles of the large arteries and arterioles hypertrophy in order to handle blood presure.	+
-	**Compromised NO? Probably, over time.	+
-	**Less distensible vessels – mechanically help cause constriction??	+
-	*Nitric oxide generation is compromised	+
-	*Vascular muscle may have a Na+- H+ antiport malfunction	+
-		+
-	====Image====	+
-	*ABout half of hypertenstives have a proportionally higher increase in bp b/c of dietary Na.	+
-	**Salt-sensitive	+
-	**If you take lots out of their diet, their bp starts heading for normal.	+
-	**BP won't improve much for non-salt-senstive	+
-		+
-	===III. Effective medical  interventions for Essential Hypertension===	+
-	*Diet restriction	+
-	*Increased Na excretion at kidney via diuretics	+
-	**Are we trading hypovolemia for hypertension?	+
-	***May not be dood?	+
-	*Decrease sympathetics	+
-	**Number of drugs do this, but it leads to exercise intolerance.	+
-	**Beta blockers	+
-	***Reduce contractility, just makes the person weak, really.	+
-	***Resistance isn't lowered.	+
-	**Alpha blockers	+
-	***Makes more physiological sense	+
-	***Decreases arterial resistance	+
-	***Decreases areterial response to norepi.	+
-		+
-		+
-	*stopped here on 01/28/2011 at 10AM.	+
-	*started here on 01/28/2011 at 11AM.	+
-		+
-		+
-	====Early essential hypertension treatment====	+
-	*Life style is so hard to change.	+
-	**Exercise and lower sodium	+
-	*Give diuretic	+
-	**Reduce vasoconstriction	+
-	**Reduce aldosterone (hence diuretic)	+
-	**Not many side effects	+
-	**ACe inhibitors:	+
-	***Causes lower resistance	+
-	***Causes lower total Na content in the body	+
-		+
-	====Late essential hypertension treatment====	+
-	*Diet and exercise	+
-	*Diuretics	+
-	*Ca cahnnel blockers	+
-	**Lower vasc resistance	+
-	**Lower contractility	+
-	**Exercise tolerability goes down	+
-	***This affects the pt's life	+
-	*Beat blockers	+
-	**Slower heart	+
-	**less contractility	+
-	**Decreased exercise toler	+
-	***Definitatley affecting their life	+
-	*Move on to Alpha-blockers	+
-	**Very compromising to pts	+
-	*Vasodilators	+
-	**Chemically relaxes vessels direclty	+
-	**Little too much and they faint	+
-	*Can really affec thte life of the pt.	+
-	**Can cause impotence, too.	+
-	*these were listed in order of application	+
-		+
-	====Side effects of hyptertensive therapy====	+
-	*Orthostatic hypotenstion	+
-	*Can't exercise / work as hard	+
-	**Get tired	+
-	**Can cause loss of job in construction, etc.	+
-	*Can't stand heat	+
-	**Because blood flow increase to skin will require more blood flow and they will get less elsewhere and get tired	+
-	*patient feels...	+
-		+
-	===Diabetes===	+
-	*Type I:	+
-	**More children have some sort of cardiac proceedures than get type I diabetes.	+
-	***So not many kids get diabetes.	+
-	**If all goes well, give insulin and the pt lives just fine.	+
-	***Oftne there are problems, though.	+
-	*Type II:	+
-	**Probably underdiagnosed	+
-	**Cause: insulin resistant	+
-	***Can have 5-10 times as much insulin	+
-	**Use "lean" not "thin"	+
-	**Treatment:	+
-	***Improve insulin secretion but that will make them more resistant; lots of pharma does this.	+
-	***Improve insulin receptor activity.	+
-	***Eventually we have to give them recombinant insulin	+
-	****Ab will be generated, unfortunately.	+
-	***Lose weight, exercise	+
-	**Prognosis:	+
-	***Good if hyperglycemia is controlled	+
-	*Obesity with insulin resistance:	+
-	**BMI > 25.	+
-	**30% of population has BMI > 30	+
-	**Causes same probs as type 2 dm but slower	+
-	***BP goes up	+
-	***atherosclerosis	+
-	**Treatment:	+
-	***diet and exercise	+
-	***emotional support; many improve with anti-depressant	+
-	***Pharma intervention: some drugs can help lose weight	+
-	**Prognosis:	+
-	***Good if weight loss occurs	+
-	***Patient compliance is a significant problem	+
-		+
-	====213 POUNDS VS 178 POUNDS====	+
-	*One gallon of fat = 7.3 pounds.	+
-		+
-	====What we used to look like====	+
-	*Cro-Magnon man by Zdenek Burian	+
-	*Little bit of a pounch.	+
-	*They ate grasses, leaves, seeds, roots, birds, small animals, fish, and some large animals.	+
-	**Roots are lousy sources of nutrition, actually.	+
-		+
-	====% men and women with hypertension vs BMI====	+
-	*As BMI increases, both men and women have significant increase in blood pressure.	+
-	*T2DM is rare in low BMIs.	+
-	*If BMI is above 30 and you're not yet T2DM, you will be in 10 years.	+
-		+
-	====FACTORS IN OBESITY  HEREDITARY====	+
-	*Since obesity is one of the strongest correlations with disease.	+
-	*Exactly what is worng in obesity is hard to say	+
-	**many theories, many genes.	+
-	*Heredity	+
-	**Some say biochem abnormalities that are genetically linked along with psychological issues that are genetically based.	+
-	*Exercise	+
-	**Exercising increases insulin sensitivity of skeletal muscle.	+
-	**Routine exercise decreases emotional stress.	+
-	**Glucose uptake is increased in the short term	+
-	**Lipids are burned when exercising.	+
-	*Food intake	+
-	**Obesity doesn't occur on healthy food.	+
-	**High in carbohydrates, usually	+
-	**Fatty foods	+
-	**Snacking is high	+
-	**Food as an emotional issue	+
-		+
-	===What does Insulin do for the vasculature?===	+
-		+
-	====EM of microvessel====	+
-	*Microvessels get torn up and are all ratty.	+
-		+
-	====Endothelial cells====	+
-	*Insulin takes about an hour to take effect beucase they have to get into the cells via vesicle, etc.	+
-	*High insulin is a good way to turn on NO.	+
-	**This hapens by activating the PKA (AKT) system which increases eNOS.	+
-	**This is good because it increases blood flow to the skeletal muscle so the muscle can take up the glucose for use later.	+
-	**This is happening all over the body, actually (brain included).	+
-		+
-	====Vascular smooth muscle cells====	+
-	*Probably don't need insuoin for glucose transport	+
-	**Use glut2 not glut4	+
-	*We don't really know what insulin does for them.	+
-	*Could be that insulin makes them healthy or helps transport aas.	+
-	*They don't need it to haveneough glucose, though.	+
-		+
-	====Graphs====	+
-		+
-	===Hyperinsulinemia===	+
-	*What happens?	+
-	**it isn't doing much good because you're resistant.	+
-	*The more resistant, the more bp goes up?	+
-	**Lack of NO?  not sure	+
-	*Something about hyperinsulinemia increases sympahtetics.	+
-	**Insulin goes trhough BBB endothelial cells	+
-	**Talks to many systems in brain cells.	+
-	*Na is retained	+
-	**Probably because symp is increased and renin / aldosterone increases	+
-	*Leptin is also elvated and icnreases bp.	+
-		+
-	====Flow chart====	+
-	*The pt gets to choose what percent of the background is expressed.	+
-	*As insluin resistance goes up, Na and Ca go up, contract too much, increased vascular resistance	+
-	*In the kidney, Na is retained, volume goes up, sympathetics go up, arterial pressure goes up.	+
-		+
-	====Atherosclerosis and insulin====	+
-	*Lots of epidemiological studys look at diabetes and BMI > 30.	+
-	*Obesity increases risk of atherosclerosis 2-3 times.	+
-	*T2DB increases risk 3-4 fold.	+
-	*Biggest problem for obese is coronary problems, strokes, peripheral vascular problems, etc.	+
-	**Have high LLDL, low HDL, and high TAGs.	+
-	**Have lots of hypertorphy, less hyperplasia, less NO.	+
-	***eNOS is expressed but signaling to use it is fubarred.	+
-		+
-	====Microvascular disease in obesity====	+
-	*Microvascular disease is rare in obesity unless you have T2DM.	+
-		+
-	====Flow chart====	+
-	*When hyperglycemic, you lose glucose and make lots of DAG.	+
-	*DAG turns on PKC:	+
-	**Phospholipases are turned on which increase DAG and IP3 such that Ca goes up, contraction of muscle goes up.  DAG also suppresses eNOS so NO is low.	+
-	**Lipid breakdown increases AA, and then prostaglandins (more constrictors like thromboxanes than dilators).  Then oxygen radicals are made and endothelial cells are damaged.	+
-	**Too many oxygen radicals destroy NO and could make peroxate nitride that permanently nitrides proteins such that they stop working.	+
-		+
-	====Glycation of enzymes====	+
-	*Some is good, some is purposeful.	+
-	*But high glucose can increase glycation and cause enzymes not to function.	+
-	*Glycated sites can also help make oxygen radicals.	+
-	*Glycation of Hb, causes Hb to not release oxygen as well in tissue.	+
-		+
-	====Image of ankle====	+
-	*Microvessels usually repair very rapidly: one day.	+
-	*In a wound they grow into it to provide blood.	+
-	*In diabetes, they don't heal or grow into wounds.	+
-	*Hence amputation is so bad in diabetes	+
-		+
-	===Outcomes of diabetes without traatment===	+
-	*REgression of microvessels, poor wound healing, amputations.	+
-	**No hair on legs as diabetics	+
-	*Accelerated atherosclerosis	+
-	*Kidney microvascular damage:	+
-	**Leaking fluid into microtubules can cause damage and decrease renal damage	+
-	*Vasospastic stroke	+
-	**When the artery spasms and stops blood to the brain.	+
-	**Ca channel blocker can help stop the spasm.	+
-	*Occlusive strokes	+
-	**Clot formationat, no blood, bad for brain	+
-	*Peripheral and sympathetic nervous sytem deteriorate	+
-	**Lots of arguments why this occurs	+
-	**Could be because nerves have limited microvascular supply so when microvascular are damaged the nerve is damaged	+
-	***Brain has better supply and they are fine in diabetes	+
-	**Peripheral Nerves, smooth muscle cells, and endothelial cells could be damaged by too much glucose (because they didn't need glucose int he first place to have neough glucose)	+
-	*Blindness	+
-	**Loss of mmicrovessels, especially caps	+
-	**Capillary overgrowth causes blindness	+
-	*Endothelial cells	+
-	**In a mess	+
-		+
-	===Clinical example===	+
-	*Injuries	+
-	*Short of breath	+
-	*Good pedal pulses (not much atherosclerosis)	+
-	*BP = 175/110	+
-	*HR = 75 / min	+
-	*Renal failure b/c of poor perfusion of the kidney	+
-	**Probably from an injury to a renal vessel.	+
-	*A. could be	+
-	*B. no because bp would have been elevated sooner in life	+
-	*C. could be but not likely	+
-	*D. no because he has good pressure in legs (coarctaction (partially occluded)	+
-	*E. he's the right age, but his bp is fine and pulmonary vascular disease usually doesn't raise his bp.	+
-		+
-		+
-	*continued on to [[Lecture 10 Coronary Artery Disease]] on 01/28/2011 at 11:50AM.	+

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Revision as of 06:18, 9 March 2012

• continued here from Lecture 8 Shock on 01/28/11 at 9:20 AM.

eTzX1x I loved your blog article.Much thanks again. Fantastic.