Advanced Patho Fall Final

What are AGEs and how do they contribute to elevated A1c? Why does it measure 3 months of glucose levels?

- Advanced glycosylation end-products (or AGEs) are proteins or lipids that, after chronic exposure to high sugars, become glycated and bound to RBCs which results in an elevated HgbA1c. - It measures 3 months because that is the lifespan of RBCs.

Clinical manifestations of hypercortisolism

- Hyperglycemia: cortisol stimulates gluconeogenesis - Collagen breakdown: part of the gluconeogenesis process and results in stretch marks. - Increases SNS activity: - Immunosuppression: cortisol decreases the # and activity of T/B cells, macrophages, neutrophils, and the release of inflammatory mediators. - Physical body changes: weight gain, round face/fat pad, central obesity, and thin extremities.

Why are diabetic individuals at increased risk of infection, especially to wounds on the feet (3 main reasons)?

- Loss of sensation via neuropathy can lead to them not noticing a wound or infection. - Atherosclerosis causes less blood to be able to reach the feet/toes → ischemic damage and decreased WBCs able to fight infection - WBC function is also impaired (mechanism not clear). - High amount of glucose gives foreign bacteria more food/energy to consume to replicate.

How does obesity contribue to HTN?

- Obesity contributes to HTN by amassing a large amount of adipose cells which release leptin. Leptin stimulates the SNS and causes Na+ reabsoprtion by the kidneys, both of which cause HTN. - Adipose tissue also releases adiponectin (which is helpful), but in obesity adipose tissue releases more leptin than adiponectin.

What are the characteristic features of metabolic syndrome and how many are needed for diagnosis?

- central obesity, dyslipidemia (high LDL and low HDL), elevated blood pressure, and elevated fasting blood glucose. - 3 of 5 are needed for diagnosis.

Describe the pathophysiological basis for polyuria in type 1 diabetes mellitus:

- glucose is normally 100% reabsorbed via a finite # of transporter proteins (tubular maximum Tm), this number correlates with a blood glucose of 180. - glucose is not reabsorbed d/t Tm → glucose stays in ureters → glucose osmotic pressure pulls water → increased excretion of water and glucose (polyuria and glucosuria) → triggers thirst centers → polydipsia.

Describe the pathophysiology of hypoxic injury in an MI

- hypoxic injury to myocardial cells -> anaerobic metabolism -> decreased ATP and lactic acid formation. - after 20min of occlusion -> irreversible injury and cell death: - Cardiac muscle cannot regenerate - intracellular K+ released -> hyperkalemia -> arrhythmia. - Ca+ release -> vasoconstriction and further damage - AG2 and catecholamine release -> vasoconstriction -> increased afterload -> increased workload and HTN.

Common etiologies of LVF/CHF

-Abnormal cardiac contraction (systolic dysfunction): myocardial ischemia/infarction, dilated cardiomyopathy, myocarditis. -Obstruction to outflow from LV: HTN -> increased LV afterload -> hypertrophy -> diastolic dysfunction -Diastolic dysfunction: MI, constrictive pericarditis, restrictive cardiomyopathy. -Limited ventricular filling: mitral stenosis -Volume overload: increased preload

Major cause of primary hypocortisolism and how it results in low cortisol?

-Anterior pituitary hypofunction (tumor, stroke...) -Special case: Suppression of ACTH by exogenous glucocorticoids can lead to hypocortisolism when medications are discontinued abruptly Decreased ACTH secretion leads to decreased cortisol secretion

Name, and give a short summary of, 6 clinical consequences of uncontrolled HTN

-Atherosclerosis: thickening and hardening of arterial wall (needs high LDL/VLDL) -Heart Failure: increased LV afterload leads to LV hypertrophy -Chronic Kidney Disease: progressive loss of renal function over time -Aneurysm: dilation or bulge in blood vessel wall -Ocular Changes: capillary damage to retina -Metabolic Syndrome: insulin resistance is developed due to increased levels of angiotensin and epinephrine.

Major cause of primary hypocortisolism and how it results in low cortisol?

-Autoimmune destruction of adrenal cortex -Familial adrenal (glucocorticoid) insufficiency (autosomal recessive disease-causing mutations in the ACTH receptors or other factors affecting ACTH signaling) -Tuberculosis Atrophy or destruction of adrenal cortex leads to decreased cortisol and aldosterone secretion (Addison disease)

Which cells are affected by shunting increased amounts of glucose through the polyol pathway in long-term poorly controlled hyperglycemia?

-CNS neurons, lens of the eye, and RBCs. -Chronic hyperglycemia causes increased glucose use in the polyol pathway → glucose being converted to sorbitol (high osmolality) → cellular swelling, injury, dysfunction, and possibly lysis.

How do AGEs contribute to microvascular disease?

-Capillary basement membrane thickening → decreased gas exchange. -Increased capillary permeability → edema -Arterial smooth muscle proliferation → arterial wall thickening/HTN -Production of oxygen-free radicals → endothelial cell injury -Inactivation of nitric oxide → vasoconstriction → HTN/ischemia -Promotion of coagulation → clot formation

Apart from cortisol, what other hormones are released during a stress response?

-Catecholamines like epinephrine and norepinephrine. -ADH which causes fluid retention -Oxytocin which promotes psychosocial bonding and attachment and is seen as a benefit of the stress process.

Describe the general functions of the following regions of the brain in relation to the stress response (cerebral cortex, amygdala, hippocampus).

-Cerebral cortex : Perceives everything that we can sense which in turn relays said information to the limbic system (amygdala, hippocampus, hypothalamus). -Amygdala: registers fear and sends projections to the hippocampus and hypothalamus. -Hippocampus: involved in short and long-term memory. It is very sensitive to cortisol which means memories are formed in stressful situations.

Clinical manifestations of right ventricular failure

-Elevated central venous pressure and JVD -Dependent pitting edema and weight gain -Hepatosplenomegaly -Consequences of decreased CO from LV

List 5 risk factors for developing dyslipidemia, and therefore, atherosclerosis.

-Genetic predisposition -High cholesterol, saturated, and trans fats diet (red meat, dairy products, and most commercial baked goods). -Sedentary lifestyle -Obesity or BMI >36 -Type 2 DM

Name 6 risk factors of HTN

-Genetic predisposition/family history -African American -Old age (>68) -High Na+ and processed food diet -Smoking & alcohol use -Obesity

List 6 causes of endothelial injury that could potentially lead to the development of atherosclerosis if a patient also had dyslipidemia.

-HTN -Tobacco use -DM -Infection -Autoimmune disease/reaction -Hyperhomocysteinemia (a molecule that, when elevated → increased LDL levels, increased blood clotting, and decreased vasodilating mediators)

Clinical manifestations of myocardial infarction and why they appear.

-HTN: due to the release of AG2 and catecolamines released -Diaphoresis: due to the activation of the SNS -Cool, clammy skin: due to decreased CO -Nausea: due to decreased CO -Fever: inflammatory response

Clinical consequences of hypocortisolism

-Hypoglycemia: lack of gluconeogenesis -Hypotension: decreased SNS activity -Bronze discoloration of skin: increased ACTH level -Fluid/electrolyte imbalances: decreased cortisol leads to aldosterone deficiency which impairs renal secretion of K+ and hydrogen ion.

Name 3 hemodynamic changes/consequences of HTN

-Increase in SVR with normal CO (most common) -Increased left ventricular afterload -Turbulence of blood causes shear stresses on vascular endothelium, leading to atherosclerosis.

Describe the role of myocardial inflammation in the development of heart failure

-Myocardial inflammation occurs from infections (bacterial, viral, etc), autoimmune disorders, cardiac trauma, medications, etc. -The result is scar tissue development of the myocardial cells. These scarred cells have a large amount of collagen in them that reduces their effectiveness making it easy for an individual to develop heart failure. Development of restrictive cardiomyopathy.

Clinical manifestations of LVF/CHF

-Pulmonary edema: SOB, respiratory acidosis, hypoxemia, tachypnea, bibasilar crackles, cough w/ frothy sputum (possibly pink if capillaries have ruptured). -Compensatory mechanisms: tachycardia, pale/cool skin, decreased urine output (aldosterone/ADH). -Hypotension: mental status changes, fatigue/weakness, and decreased urine output.

Major causes of secondary hyperthyroidism and its result

-TSH-secreting pituitary adenomas -Graves disease -Overdose of thyroid medication - Results in increased TSH section → increased T3/4

Define type 1 A/B DM and their causes.

-Type 1A: Autoimmune-mediated type 1 DM. beta-cell destruction leads to insulin deficiency, autoantibodies, and cytotoxic T cells target beta cells, insulin, and antigens in pancreatic islets. (B/T lymphocyte process). -Caused by: genetics (18 genomic locations, parent or sibling = 10% more likely to develop), viral infections, and diet. -Type 1B: Nonimmune-mediated type 1 DM. beta-cell destruction but usually caused by an outside source rather than the immune system. -Caused by: diseases such as pancreatitis and cystic fibrosis.

What are tyrosine kinase and GLUT-4 and what role do they play in insulin-mediated glucose uptake?

-Tyrosine kinase is an enzyme that activates intracellular enzymes which stimulate cellular physiological effects like the uptake of glucose. - insulin binds to cell insulin receptor → tyrosine kinase activates → activates intracellular enzymes → cellular reuptake of glucose via the GLUT4 proteins (and other actions). - GLUT4 is a transport protein that is required for the diffusion of glucose into the cells.

What are the major causes of primary hypercortisolism and how do they result in elevated cortisol?

-adrenal adenoma/carcinoma -non-adrenal tumor synthesizes and secretes cortisol -administration of cortisol-like medications (hydrocortisone, prednisone, etc) increased cortisol → decreased ACTH

Major causes of primary hyperthyroidism and its result

-genetic predisposition -thyroiditis -toxic nodular/multinodular goiter (Plummer disease) -Thyroid adenomas or benign growths -Thyroid cancer (usually one-sided) - All result in increased T3/4 secretion

Discuss how insulin resistance develops in type 2 DM. (2 factors)

-genetics and/or high caloric diet causes hyperinsulinemia → down-regulation of insulin receptors and chronically high insulin levels → few functional receptors are able to respond to insulin → insulin resistance. -obesity → more adipose tissue → increased release of adipokines which stimulate insulin resistance → increased insulin resistance.

Describe the compensatory mechanisms that help maintain blood pressure despite a low cardiac output in left ventricular failure

-low BP → activation of the SNS system results in increased HR and LV contractility (or so it attempts to do so) and vasoconstriction → increased SVR. -low BP → renal compensation via aldosterone and ADH secretion → attempt to increase blood volume.

What are the major causes of secondary hypercortisolism and how do they result in elevated cortisol?

-pituitary adenomas with hypersecretion of ACTH (75-80% of cases) -non-pituitary tumor synthesizes and secretes ACTH. increased ACTH → increased cortisol and androgens.

Describe the variety of physiological actions or effects that insulin has on cells.

-promotes glucose storage as glycogen. -inhibits glucose-producing pathways. -fatty acid synthesis and triglyceride formation (phospholipids) -transports amino acids into cells and stimulates protein synthesis -stimulates cell growth and differentiation -facilitates K+ transport into cells.

Draw the pathophysiological pathway of endothelial injury and hyperlipidemia leading to obstruction of blood vessels and ruptured plaque.

(drawing)

How does a stressor result in cortisol secretion from the adrenal cortex?

A stressor is sensed by the cerebral cortex and information is then relayed to the hypothalamus → release of corticotropin-releasing hormone (CRH) → adrenocorticotropic hormone (ACTH) is released into the bloodstream → ACTH reaches the adrenal glands which signal an increase in cortisol production.

A new patient presents with some of the physical changes associated with hypercortisolism. You order a blood draw and get the following results: AM plasma cortisol levels = 48 mcg/dL (high) and plasma ACTH levels of 4 pig/ml (low). Which is the most likely cause of this patient's endocrine imbalance? A tumor in the hypothalamus A tumor in the adrenal cortex A pituitary stroke A pituitary tumor

A tumor in the adrenal cortex

What are adipokines and how do they contribute to the development of DM in obese individuals?

Adipokines are hormones/cytokines produced by the adipose tissue. -obesity → more adipose tissue → increased release of adipokines which stimulate insulin resistance → increased insulin resistance. -also increase secretion of glucagon causing hyperglycemia.

Define the concept of allostatic load and the four main factors that contribute to the negative effects of high allostatic load over a lifetime.

Allostatic Load is the collective stress an individual experiences over a long period of time that causes wear and tear on the body via the constant exposure of cells and tissue to stress hormones (which can alter cell function) -Exposure to multiple stressors over time -Failure to habituate to repeated stressors -Delayed shutdown of stress response -Inadequate stress response that leads to compensation from other mediators

Which of the following hormones/neurotransmitters stimulate arterial vasoconstriction to maintain systemic vascular resistance and blood pressure? (Choose 2 responses) Angiotensin II Nitric oxide Aldosterone Norepinephrine BNP

Angiotensin II and Norepinephrine

Does primary or secondary hyperthyroidism cause the development of a goiter? Why?

Any secondary hyperthyroidism that increases TSH secretion because that will increase follicle growth → increase in follicle # and gland size.

Why is an elevation in the plasma levels of B-type natriuretic peptide (BNP) an indication that a patient may have heart failure? BNP is released when the there are increased residual volumes leading to increased preload or when the kidneys retain fluid to compensate for the drop in CO and blood pressure. Elevated BNP levels are a common cause of hypertension which often leads to heart failure. Elevated BNP is a common cause of fluid overload which exacerbates heart failure. BNP is released whenever stroke volumes decrease.

BNP is released when the there are increased residual volumes leading to increased preload or when the kidneys retain fluid to compensate for the drop in CO and blood pressure.

Describe BNP secretion in LVF/CHF

BNP is stimulated by ventricular stretch/dilation caused by: increased LV preload and/or renal retention of fluid. Its role is to dilate blood vessels and cause kidney to excrete Na+ and water.

Why is CK-MB elevated following MI?

CK-MB is an enzyme found in myocardial muscle cell that is released after injury. CK-MB rises 4-6hrs after MI, peaks in 24hrs, and disappears in 2-3 days.

Why is CRP elevated following MI?

CRP is a protein released by the liver during inflammation CRP is a good predictor of mortality following an acute MI but lacks specificity because it is a marker for general inflammation.

Why is an elevated CRP an early indicator and predictor of coronary artery disease?

CRP is an indication of inflammation. CAD can cause inflammation throughout the vasculature in the body.

If left untreated, why is hypertension caused by increased catecholamines and angiotensin II difficult to reverse?

Catecholamines and AG2 cause the narrowing of blood vessels which causes HTN. It is difficult to reverse because the arteries develop fibrosis and become permanently contracted and unable to dilate to relieve high BP.

Shunting of glucose to the polyol pathway and the build up of sorbitol and fructose causes damage to which of the following cells? White blood cells and renal tubular cells Muscle and skin cells Endothelial and liver cells Cells in the lens of eye and neurons

Cells in the lens of eye and neurons

List 5 non-cardiac conditions that could precipitate a myocardial infarction. (2 classes)

Conditions that increase metabolic demand: -extreme physical demand -HTN -aortic stenosis Conditions that reduce O2 content of the blood: -hypoxemia (high altitude/pulmonary disease) -anemia

What is the most common cause of myocardial infarction?

Coronary athersclerosis or CAD

Describe the pathophysiology of decreased Nitric Oxide production that leads to HTN (include hormones and neurotransmitters).

Decreased NO production (ERDF) causes HTN because NO is a vasodilator, therefore it cannot help counter vasoconstrictive effects.

Describe the mechanisms that cause pulmonary edema in left ventricular failure.

Decreased O2 to LV -> decreased contractility -> decreased CO/ejection fraction -> increased residual volumes in LV -> increased LV preload -> backup of pressures into pulmonary veins/capillaries -> pulmonary edema.

Describe the general pathophysiology of hemodynamic changes in LVF (CHF).

Decreased cardiac output -> increased residual volumes in LV aka increased LV preload... Decreased cardiac output -> decreased BP -> SNS activation and renal compensation...

Draw a table showing how decreased o2 delivery to the LV ends in worsening LV function and HF.

Diagram on CV3 notes

In addition to hyperglycemia, what other condition often develops in type 2 diabetics? a. Chronic pancreatitis b. Liver cirrhosis c. Cancer d. Dyslipidemia

Dyslipidemia

Which of the following laboratory indicators can be used to predict the risk of death from cardiovascular disease in the weeks and months following an acute MI? Elevated CRP Elevated CK-MB Elevated troponin T Elevated LDH

Elevated CRP

How does chronic stress lead to depression and anxiety disorders? Elevated CRH stimulates apoptosis on neurons in the amygdala. Elevated norepinephrine is directly linked to depression and anxiety. Elevated cortisol inhibits serotonin production in the brain. Elevated cortisol causes down regulation of serotonin receptors in the brain.

Elevated cortisol inhibits serotonin production in the brain.

How does chronic stress cause fertility issues? Elevated cortisol leads to LH inhibition and suppression of ovulation. Elevated thyroid hormone causes a rise in metabolic rate that damages the ovum. Elevated epinephrine makes the endometrium an inhospitable tissue for implantation. Elevated cortisol stimulates estrogen and progesterone secretion which blocks ovulation.

Elevated cortisol leads to LH inhibition and suppression of ovulation.

Why do individuals with Cushing disease or syndrome develop a thinning of the dermis that leads to pressure ulcers? Elevated cortisol inhibits gluconeogenesis in the epidermis Elevated ACTH causes the breakdown of skin tissue Elevated ACTH causes lipolysis in pressure areas such as the buttocks Elevated cortisol promotes the breakdown of collagen in the dermis

Elevated cortisol promotes the breakdown of collagen in the dermis

Which lab test is the best indirect measure of the presence of atherosclerosis in any artery? Elevated erythrocyte sedimentation rate (ESR) Troponin I Elevated high sensitivity C reactive protein (hs-CRP) High LDLs

Elevated high sensitivity C reactive protein (hs-CRP)

What pathologic changes in patients with hypertension contribute to the development of chronic renal failure (i.e., chronic kidney disease)? High glomerular pressures leads to increased filtration and reduced time for reabsorption. Endothelial injury in the renal arteries leads to atherosclerosis and decreased blood flow to the kidneys. Release of angiotensin II causes direct injury to the renal tubules. The genetic mutations that cause hypertension also cause renal failure.

Endothelial injury in the renal arteries leads to atherosclerosis and decreased blood flow to the kidneys.

Why is type 2 diabetes a risk factor for dyslipidemia (select 2) Excess glucose is converted into lipids by the liver Hyperglycemia causes endothelial injury Insulin resistance promotes the conversion of HDL to LDL The liver synthesizes increased amounts of VLDLs

Excess glucose is converted into lipids by the liver The liver synthesizes increased amounts of VLDLs

An acute insulin deficiency causes potassium to shift into cells resulting in hypokalemia. True/False

False

Why is it important that glucose is stored as glycogen?

Glycogen does not have the osmotic effect that glucose does.

Unique clinical manifestations of Graves' disease and why they occur.

Goiter formation: due to the TSH-like effects of TSI and TSI accumulation in thyroid gland. exophtalmos and extraocular muscle dysfunction due to the effects of TSI.

Why is HDL considered 'good' cholesterol? HDL cleanses the liver so that other lipoproteins do not accumulate. HDL binds to and helps reduce the 'bad' cholesterol. HDL coats the blood vessels and protects the endothelium from saturated fats. HDL is a lipoprotein that can remove cholesterol from the tissues or an atherosclerotic lesion.

HDL is a lipoprotein that can remove cholesterol from the tissues or an atherosclerotic lesion.

What role does the hippocampus area of the limbic system play in the stress response? Hippocampal neurons release catecholamines and dopamine, which heighten the stress response in the brain. Hippocampal neurons are responsible for memories that can affect how a person responds to stress. Neuroendocrine cells in the hippocampus release CRH and other stress hormones. The hippocampus contains neurons that sense stress.

Hippocampal neurons are responsible for memories that can affect how a person responds to stress.

Negative effects of catecholamines during a stress response include all of the following EXCEPT: Increased levels of plasma lipids leading to atherosclerosis. Vasoconstriction of systemic arteries leading to hypertension. Hyperactivity of intestinal smooth muscle leading to diarrhea. Elevation of plasma glucose levels leading to metabolic syndrome.

Hyperactivity of intestinal smooth muscle leading to diarrhea.

Why is hypertension a risk factor for the development of atherosclerosis in the aorta and other large arteries? Hypertension causes turbulent blood flow which can cause endothelial injury. Hypertension leads to the production of free radicals that cause endothelial injury. Hypertension is a risk factor for dyslipidemia. Hypertension leads to peripheral ischemia which causes endothelial injury.

Hypertension causes turbulent blood flow which can cause endothelial injury.

Describe the pathophysiology of reprefusion injury in an MI

Hypoxic cells produce xanthine oxidase -> turns reintroduced O2 into oxygen free radicals Reintroduction of WBCs -> further inflammation

How can left ventricular failure lead to right ventricular failure?

Increased LV and LA pressure push back into pulmonary circulation → increased pulmonary vascular resistance/pressure → increased RV afterload → myocardial hypertrophy → decreased filling volumes → diastolic dysfunction.

Why does long term primary (systemic) hypertension eventually lead to left ventricular failure? Increased afterload leads to left ventricular hypertrophy and diastolic dysfunction. Oxygen delivery to the left ventricle is reduced because of the high blood pressures The left ventricle gradually dilates due to the high systemic blood pressures Hypertension is a common cause of valve disease.

Increased afterload leads to left ventricular hypertrophy and diastolic dysfunction.

Which of the following metabolic changes are indicative of hyperthyroidism? a. Increased body temperature and hot flashes b. Orthostatic hypotension c. Poor appetite d. Weight gain

Increased body temperature and hot flashes

Why do patients with left ventricular failure (LVF) experience dyspnea and hypoxemia? Increased hydrostatic pressures in the pulmonary capillaries leads to pulmonary edema. Inflammation in the lungs causes pulmonary edema. Decreased cardiac output causes a reactive bronchoconstriction. Patient with LVF are prone to developing spontaneous pneumothorax.

Increased hydrostatic pressures in the pulmonary capillaries leads to pulmonary edema.

In response to decreased cardiac output and blood pressure in LVF, the sympathetic nervous system is activated. Which of the following is a negative effect of this compensatory mechanism? Increased left ventricular afterload. Increased left ventricular preload. Reduced Frank-Starling effect. Rebound bradycardia.

Increased left ventricular afterload.

Which of the following hemodynamic changes occur in left ventricular failure (LVF) that is systolic in nature? Increased left ventricular preload Decreased systemic vascular resistance Decreased right ventricular afterload Increased venous return to right ventricle

Increased left ventricular preload

In response to decreased cardiac output and blood pressure in LVF, renal compensation mechanisms are activated. Which of the following is a negative effect of this compensatory mechanism? Increased left ventricular preload and ventricular dilation Diuresis leading to dehydration. Anemia. Decreased oxygen delivery to the myocardium.

Increased left ventricular preload and ventricular dilation

Which of the following conditions is the most potent stimulus for insulin secretion by the pancreas? a. Increased plasma amino acid levels b. Decreased plasma glucose levels c. Increased sympathetic stimulation d. Decreased plasma lipid levels

Increased plasma amino acid levels

Why does right ventricular failure lead to hepatosplenomegaly? The liver hypertrophies in response to chronically high portal venous pressure Red blood cell function becomes impaired, resulting in hemolysis in the spleen and splenic congestion Increased right ventricular preload results in a back up of pressures into the systemic veins including the IVC, portal system, and spleen Right ventricular failure stimulates an inflammatory response and the inflammatory mediators cause damage to the liver and spleen

Increased right ventricular preload results in a back up of pressures into the systemic veins including the IVC, portal system, and spleen

How would a gene mutation leading to increased aldosterone levels cause hypertension? Increased feedback to the sympathetic nervous system causes tachycardia. Increased water reabsorption by the kidneys causes hyponatremia. Increased sodium and water reabsorption by the kidneys leads to fluid retention. Increased renal excretion of sodium leads to water retention.

Increased sodium and water reabsorption by the kidneys leads to fluid retention.

Why do individuals with type I diabetes mellitus produce ketones? a. Insulin deficiency leads to the breakdown of protein in muscle tissue. b. Insulin deficiency leads to the breakdown of fat/lipids in adipose tissue. c. Exogenous insulin administration causes the release of ketones from the liver. d. Destruction of the endocrine pancreas causes the release of ketones into the bloodstream.

Insulin deficiency leads to the breakdown of fat/lipids in adipose tissue.

Major causes of primary hypothyroidism and its result

Iodine deficiency congenital lack of thyroid tissue Hashimotos loss of thyroid tissue → decreased T3/4

When compared to type 1A diabetes mellitus, type 1B diabetes mellitus: (Select the response that IS a characteristic of type IB diabetes mellitus) a. Is not caused by autoimmunity b. Is characterized by insulin resistance c. Results in elevated serum c-peptide levels d. Is characterized by elevated insulin levels

Is not caused by autoimmunity

Describe the range of neurological deficits seen in diabetic neuropathy.

Ischemia of peripheral neurons, axonal degeneration, and demyelination of neurons → sensory deficits (usually in feet and bilaterally), motor deficits (alterations in gait, strength, and motor coordination), and autonomic dysfunction (diarrhea and orthostatic hypotension)

Why is LDH-1 elevated following MI?

LDH-1 is an isoenzyme found in cardiac muscle cells. It is a good late indicator of myocardial cell injury, rising at 24-72hrs, peaks at 3-4 days, returns to normal 8-14 days.

The accumulation of which molecule causes ischemic pain in a myocardial infarction? Creatine-kinase Lactic acid Lactate dehydrogenase Calcium

Lactic acid

Which of the following problems is most likely to cause a deterioration in cardiac function in individuals with coronary artery disease? Low plasma hemoglobin (anemia) Elevated plasm a glucose (hyperglycemia) Elevated plasma sodium (hypernatremia) Cerebral hypoxia (stroke)

Low plasma hemoglobin (anemia)

How is the metabolic rate affected by thyroid, hyperthyroid, and hypothyroid? (and manifestations).

Metabolic rate is stimulated by T3/4. -Hyperthyroid: heat intolerance and weight loss -Hypothyroid: cold intolerance and weight gain

The daily hassles of life that cannot be avoided are classified as what type of stressor? Chronic stressor Life stressor Microstressor Acute stressor

Microstressor

Myocardial ischemia vs myocardial infarction

Myocardial Ischemia: A partial impairment of coronary artery blood flow and oxygen delivery to cardiac tissue -Stable Ischemia: impaired ability to deliver blood to the cardiac tissue during exercise->starves the tissue from needed oxygen -> results in angina (chest pain) -Unstable Ischemia: more severe in that it occurs also at rest or during little exertion- warning sign of a possible heart attack Myocardial Infarction: complete obstruction of blood flow to cardiac tissue- results in tissue death or necrosis- also known as a heart attack

Which of the following are considered to be common complications of DM caused by macrovascular disease? Myocardial infarction and stroke Anemia and leukopenia Liver cirrhosis and pancreatitis Diabetic ketoacidosis and hyperosmolar nonketotic syndrome

Myocardial infarction and stroke

Why is myoglobin elevated following MI?

Myoglobin is a protein released after myocardial cell injury. Not very specific to acute MI

How does inflammation contribute to the pathophysiology of acute myocardial infarction? (choose 2): Neutrophilic phagocytosis results in the release of damaging reactive oxygen species and lysosomal enzymes Autoantibodies become activated that opsonize cardiac cells and attract neutrophils to the area for phagocytosis The activation of the complement system results in the development of a membrane attack complex (MAC) that directly injures myocardial cells Myocardial cells are injured by inflammatory mediators

Neutrophilic phagocytosis results in the release of damaging reactive oxygen species and lysosomal enzymes Myocardial cells are injured by inflammatory mediators

Describe the pathophysiology of inflammation in an MI

Neutrophils release inflammatory mediators and reactive oxygen species -> myocardial cell injury.

How does activation of the sympathetic nervous system help the body maintain blood pressure in left ventricular failure? Norepinephrine stimulates alpha-1 receptors which results in arterial vasoconstriction. Epinephrine stimulates the ventricles to contract with more force. Catecholamines stimulate sodium and water reabsorption which increases blood volume. Epinephrine helps reverse the negative effects of myocardial hypoxia.

Norepinephrine stimulates alpha-1 receptors which results in arterial vasoconstriction.

Describe how primary pulmonary hypertension leads to right ventricular failure

PPH is caused by vasoconstriction due to endothelial dysregulation and/or fibrosis of pulmonary arteries → hypertrophy of smooth muscle in vessel walls → increased pulmonary vascular resistance → increased RV afterload → myocardial hypertrophy → decreased filling volumes → diastolic dysfunction.

Why is obesity associated with the development of hypertension? Pathologically hypertrophied adipose cells release leptin which stimulates arterial vasoconstriction. Intra-abdominal adipose tissue causes pressure on the aorta and intra-abdominal arteries. Adipose cells release ADH causing water retention. Most cases of hypertension in obese individuals is due to atheroslerosis in the aorta.

Pathologically hypertrophied adipose cells release leptin which stimulates arterial vasoconstriction.

Compare and contrast lab findings (TSH and T3/4) in primary, secondary, and Graves' disease.

Primary: decreased TSH and increased T3/4 because the body recognizes there is too much and is trying to slow down production. Secondary: increased TSH and increased T3/4 because TSH is being stimulated by an outside cause (adenoma, medication). Graves: decreased TSH and increased T3/4 because of the production of TSI, which has the same effect as TSH while TSH is being suppressed.

Compare and contrast lab findings (TSH and T3/4) in primary and secondary hypothyroidism.

Primary: increased TRH and TSH, decreased T3/4... the hypothalamus recognizes there is a lack of T3/4 → increases TSH → TSH acts on the pituitary to release T3/4 → there isn't enough tissue to recover T3/4 levels. Secondary: decreased TSH and decreased T3/4... the hypothalamus is not able to signal the pituitary appropriately resulting in low T3/4 levels.

Which of the following correctly describes the pathophysiology of Graves disease? Ectopic production of thyroid hormone by a malignant tumor Overproduction of TSH by the anterior pituitary gland Autoimmune destruction of the thyroid follicle Production of antibodies that mimic TSH function

Production of antibodies that mimic TSH function

Left ventricular failure resulting from right ventricular failure will result in all of the following clinical manifestations EXCEPT Pale, cool skin and mottling Decreased urine output Hypotension and tachycardia Pulmonary edema

Pulmonary edema

Why does chronic left ventricular failure (LVF) eventually cause right ventricular failure (RVF)? Blood flow from the vena cavas into the right atrium and ventricle is reduced. Decreased pulmonary vascular resistance increases RV preload. Pulmonary hypertension from LVF causes right ventricular hypertrophy. Cardiac output from the LV to the RV is reduced.

Pulmonary hypertension from LVF causes right ventricular hypertrophy.

An infarction of which coronary artery will lead to right ventricular myocardial infarction (and likely some degree of right ventricular failure)? Circumflex artery Right coronary artery Left coronary artery Left anterior descending artery

Right coronary artery

All of the following are true about right ventricular afterload EXCEPT increased pulmonary vascular resistance leads to increased right ventricular afterload In the setting of chronically increased right ventricular afterload (pulmonary HTN), the right ventricle will attempt to hypertrophy to compensate Right ventricular afterload relates to the volume of blood in the right ventricle Right ventricular afterload increases in the setting of pulmonary hypertension

Right ventricular afterload relates to the volume of blood in the right ventricle

How can right ventricular failure lead to left ventricular failure? Right ventricular failure causes pulmonary edema, which results in decreased oxygen delivery to the heart Right ventricular cardiac output decreases so there is decreased blood delivery to the left ventricle Right ventricular failure causes a back-up of pressures in the systemic arteries, increasing left ventricular afterload Right ventricular failure leads to the development of a blood clot that blocks the left coronary artery

Right ventricular cardiac output decreases so there is decreased blood delivery to the left ventricle

Normal metabolic effects of insulin include all of the following EXCEPT: a. Increasing glucose uptake by the liver. b. Stimulating amino acid uptake and protein synthesis in skeletal muscle cells. c. Stimulating fat breakdown in the adipose tissues. d. Promoting glycogen storage in skeletal muscle cells.

Stimulating fat breakdown in the adipose tissues.

Which of the following blood vessels will experience an increase in pressure due to right ventricular failure? Systemic veins Systemic arteries Pulmonary veins Pulmonary arteries

Systemic veins

How is the cardiovascular system affected by thyroid, hyperthyroid, and hypothyroid? (and manifestations).

T3/4 increases cell responsiveness to catecholamines like epinephrine and norepinephrine. -Hyperthyroid: HTN from vasoconstrictive SNS effects. -Hypothyroid: Hypotension from decreased SNS effects.

How is the nervous system affected by thyroid, hyperthyroid, and hypothyroid? (and manifestations).

T3/4 promotes normal maturation of the nervous system. -Hyperthyroid: hyperactive reflexes from increased T3/4 causes heightened neuromuscular sensitivity. -Hypothyroid: hypoactive reflexes from decreased T3/4 causes lower neuromuscular sensitivity.

All of the following are true about the role of the cerebral cortex in the stress response EXCEPT: The cerebral cortex is responsible for creating and storing memories that can contribute to future perception of stress The cerebral cortex is responsible for routing information to the limbic system The cerebral cortex helps to triage the information collected by the sensory organs to determine if a threat exists The area of the cerebral cortex involved in receiving sensory information is called the somatosensory cortex

The cerebral cortex is responsible for creating and storing memories that can contribute to future perception of stress

An 74 year-old-male who presents to the ED with chest pain, nausea and syncope is diagnosed as having an acute myocardial infarction. In the cardiac catheterization lab, two stents are placed in branches of the left coronary artery. On follow up, there is evidence of necrotic cardiac muscle tissue. It is suspected that the cardiac reperfusion contributed to this injury. What is the primary cause of reperfusion injury? Rapid oxygen uptake by hypoxic cells overwhelms the mitochondria causes cell dysfunction. The reintroduction of K+ into the tissues causes severe dysrhythmias. The formation of xanthine oxidase in hypoxic tissue causes the formation of free radicals when oxygen is reintroduced. The reintroduction of Na+ causes rapid Na+ uptake and cell swelling/lysis.

The formation of xanthine oxidase in hypoxic tissue causes the formation of free radicals when oxygen is reintroduced.

How does activation of the renin-angiotensin-aldosterone system help the body maintain blood pressure in left ventricular failure? The hormones released increase systemic vascular resistance and blood volume. The hormones released stimulate the heart to contract with more force. The hormones released help resolve the edema. The hormones released help to reduce myocardial workload.

The hormones released increase systemic vascular resistance and blood volume.

Systolic vs Diastolic heart failure

The inability of the ventricle to contract against a load resulting in decreased ejection fraction and increased left ventricular end diastolic volume (LVEDV) or decreased ventricular contractility during systole. An impairment in left ventricular filling which results in decreased CO or decreased ability of the ventricle to stretch and fill during diastole.

What does the term allostatic load refer to in the stress response? A person's perception of a stressful event. The inability of the brain to cope with stress. The negative effects of chronic or repeated stress over time. The body's reaction to anticipatory stress.

The negative effects of chronic or repeated stress over time.

What is the most common cause of type 1A diabetes mellitus? a. An autoimmune response against insulin receptors. b. The production of antibodies and T cytotoxic cells that target the beta cells and insulin. c. Childhood obesity resulting in hyperglycemia and hyperinsulinemia. d. A congenital absence of pancreatic beta cells caused by a single gene mutation.

The production of antibodies and T cytotoxic cells that target the beta cells and insulin.

The symptom of polyuria in diabetes mellitus is best explained by which of the following mechanisms? a. The renal threshold for glucose filtration in the glomerulus is reached. b. The presence of ketones attracts large volumes of water into the urine filtrate. c. An insulin deficiency stimulates the kidneys to secrete excess glucose and water into the renal tubules. d. The tubular maximum for glucose reabsorption is reached which stimulates the process of osmotic diuresis.

The tubular maximum for glucose reabsorption is reached which stimulates the process of osmotic diuresis.

You are evaluating a 72 year old woman in the post-acute care setting who was recently admitted following hospital discharge for CHF exacerbation. You review her daily weights and note that she has gained 4 lbs since yesterday. On examination, she has 2+ pitting edema in bilateral lower extremities. Why has this peripheral edema developed? There is increased hydrostatic pressure in the peripheral capillaries as a result of increased right ventricular preload There is decreased blood volume, so blood is unable to return to the heart. The valves in the peripheral veins have failed due to shear forces There is decreased left ventricular cardiac output as a result of increased left ventricular afterload

There is increased hydrostatic pressure in the peripheral capillaries as a result of increased right ventricular preload

Which of the following is a common factor contributing to the development of myocardial infarction? Embolization of plaque from the aorta Decreased ventricular diastolic filling time Dysplasia of the muscle layer of the coronary artery Thrombus formation within the atherosclerotic coronary artery

Thrombus formation within the atherosclerotic coronary artery

Why is Troponin I (not K) elevated following MI?

Troponin I is a contractile protein that is only found in the blood when myocardial necrosis occurs. Troponin K is found in both cardiac and skeletal muscles.

Chronic exposure to the compensatory hormones released in chronic LVF leads to disengagement of actin and myosin molecules that contributes systolic dysfunction. True/False

True

The most critical factor when considering whether or not a given stimulus will cause a stress response is the individual's perception of the stimulus. True/False

True

Why are long-term diabetics at a high risk for developing infected wounds on the bottom their feet? (Choose all that apply) Bone marrow failure is a common consequence of diabetes. IgA levels are reduced in diabetics. White blood cells function is impaired by chronic hyperglycemia. Bacterial growth is promoted by hyperglycemia

White blood cells function is impaired by chronic hyperglycemia. Bacterial growth is promoted by hyperglycemia

Which of the following is true about right ventricular failure as a result of chronic pulmonary disease? Chronic pulmonary disease is an independent risk factor for primary pulmonary hypertension, which leads to right ventricular failure Chronic hypoxemia causes pulmonary arteriole vasodilation With pulmonary disease, hypoxemia leads to decreased oxygen delivery to the heart, which impairs right ventricular contractility Chronic impaired gas exchange can result in decreased right ventricular afterload

With pulmonary disease, hypoxemia leads to decreased oxygen delivery to the heart, which impairs right ventricular contractility

Metabolically, glucocorticoids such as cortisol, cause: a rise in blood glucose levels. muscle building. fat storage throughout the body glucose utilization in muscles.

a rise in blood glucose levels

How does insulin regulate blood glucose levels? (include factors that stimulate their secretion - alpha cells)

alpha cells in Islets of Langerhans are stimulated → release of glucagon → increased glycogenolysis and gluconeogenesis → increased blood glucose. Stimulated by: decreased blood glucose.

All of the following conditions may precipitate a myocardial infarction by increasing myocardial demand, EXCEPT: aortic stenosis. extreme physical exertion. hypertension. anemia.

anemia

Why do type 2 diabetics with poor glycemic control often require insulin to treat their hyperglycemia?

because of down-regulation and high insulin, the body begins to slow down insulin production, and eventually, insulin is once again needed.

The vast majority of cases of hypercortisolism are caused by: a. genetic mutations that cause congenital Cushing's disease or syndrome. b. complicated pregnancy. c. benign and malignant tumors of the pituitary gland and adrenal cortex. d. autoimmune disease.

benign and malignant tumors of the pituitary gland and adrenal cortex.

Describe the pathophysiological basis for hyperglycemia in type 1 diabetes mellitus:

beta cell destruction (80-90% of beta cells are destroyed before seeing manifestations) → no more insulin production → increased glucose in the blood.

How does insulin regulate blood glucose levels? (include factors that stimulate their secretion - beta cells)

beta cells in Islets of Langerhans are stimulated → synthesis/secretion of insulin → insulin binds to cells → reuptake of serum glucose into the cells. Stimulated by: high blood glucose, amino acid, free fatty acid levels, GI hormones (gastrin CCK and secretin), and parasympathetic stimulation.

Why is heart failure caused by CAD considered to not be 'curable'?

by the time heart failure is diagnosed, the individual has been exposed to elevated levels of catecholamines, angiotensin 2, aldosterone, other hormones and inflammatory mediators for potentially many years causing cardiovascular injury like ventricular hypertrophy and interstitial fibrosis.

What is myxedema? What symptoms of hypothyroidism are directly related to myxedema?

collagen in connective tissue is replaced by proteins and mucopolysaccharides creating swelling of the skin. symptoms: hypotension, bradycardia, cold intolerance, goiter, low energy/lethargy, weight gain, and weakness.

Describe the SNS response to decreased CO.

decreased CO in LV -> decreased BP -> SNS activation (2 pathways) 1: increase HR (beta-1) 2: vasoconstriction (alpha-1) -> increased SVR -> increased LV afterload -> increased myocardial workload

Describe renal compensation to decreased CO.

decreased CO in LV -> decreased BP -> renal compensation -> Aldosterone/ADH secretion -> increased LV preload -> increased myocardial workload

Why does chronic hypoxemia associated with chronic pulmonary disease eventually lead to right ventricular failure?

decreased gas exchange in the lungs leads to hypoxemia → vasoconstriction of the pulmonary arteries and decreased O2 delivery to heart tissue → increased PVR → increased RV afterload → RV dilation/hypertrophy → decrease RV CO/EF.

Draw pathway from chronic pulmonary disease to peripheral edema and LV failure

diagram on CV4 notes.

The pathophysiology of type 2 diabetes mellitus (DM) primarily involves: a. increased renal reabsorption of glucose. b. down regulation of insulin receptors. c. beta cell destruction. d. reduction in glucagon synthesis.

down regulation of insulin receptors.

Which of the following is NOT a theory explaining why non-Hispanic Black individuals in the United States have increased incidence of hypertension and greater risk of related complications when compared to individuals from other racial and ethnic groups? poor maternal nutrition. therapeutic inertia. gene mutations causing increased risk of renal artery stenosis. dietary factors.

gene mutations causing increased risk of renal artery stenosis.

Discuss how insulin resistance contributes to hyperglycemia and dyslipidemia in type 2 DM.

hyperglycemia: insulin function is inhibited → decreased serum glucose uptake → hyperglycemia. dyslipidemia: insulin resistance develops → lipolysis activity increases → fatty acids are released into the bloodstream → dyslipidemia (high LDL, low HDL) is usually present at diagnosis of type 2 DM.

All of the following clinical consequences are associated with long term, untreated hypothyroidism EXCEPT: hyperreflexia and anxiety anemia. confusion, memory loss and other cognitive changes. hypoxemia and hypercapnea.

hyperreflexia and anxiety

Unstable angina is a sign of: impending myocardial infarction. electrical conduction problems in the heart. mild to moderate atherosclerosis. decreased myocardial oxygen demand.

impending myocardial infarction.

Describe the pathophysiology of increases SNS activity that leads to HTN (include hormones and neurotransmitters).

increased SNS activity causes the chronic release of catecholamines epinephrine and norepinephrine. Epi and norepi (mostly norepi) act on alpha-1 adrenergic receptors in arteries → vasoconstriction → increased SVR and HTN. Beta-1 receptors in SA node of the heart lead to increased HR, SV, and CO.

Negative effects of cortisol during a stress response include all of the following EXCEPT: increased urine output leading to dehydration. increased catecholamine release leading to hypertension. stimulation of gastric secretions resulting in peptic ulcer disease. elevated plasma glucose leading to type 2 diabetes mellitus.

increased urine output leading to dehydration.

Why is fluid overload problematic for individuals with heart failure?

increased venous return to heart → increased preload → ventricular dilation → ventricular dysfunction and the HF patients are unable to compensate for more volume.

How does long-term, uncontrolled hypertension often lead to left ventricular dysfunction?

long-term HTN → increased LV afterload → myocardial hypertrophy → increased wall thickness and decreased ventricular compliance → decreased filling volumes → diastolic failure. Increased LV afterload also → if LV afterload > pressures generated during systole → systolic failure.

All of the following are direct causes of right ventricular failure (RVF) EXCEPT: mitral stenosis. chronic obstructive pulmonary disease (COPD). a large pulmonary embolus. primary pulmonary hypertension.

mitral stenosis

Describe the pathophysiological basis for weight loss in type 1 diabetes mellitus:

muscle, fat, and water/fluid loss.

In general, coronary artery disease (CAD) leads to: an increase in myocardial workload. hypoxemia. myocardial ischemia. coronary artery vasoconstriction.

myocardial ischemia.

During a stress response, the locus ceruleus region of the brainstem produces ________ which heightens activity in the brain. oxytocin cortisol corticotropin releasing hormone norepinephrine

norepinephrine

The fatty streak in the wall of an artery that has developed atherosclerosis is formed by: injured neutrophils that accumulate HDL. lipid-laden mast cells. oxidation of LDL by macrophages. deposited adipose cells.

oxidation of LDL by macrophages.

What is afterload? What can increased LV afterload lead to?

pressure against the LV that it needs to overcome to pump blood from the LV. Increased LV afterload causes the heart to have to work to overcome the increased pressure → myocardial hypertrophy (heart muscle gets larger) → ventricle space eventually decreases → CO and contractility decrease.

Metabolic syndrome, an important risk factor for type 2 DM, is characterized by an elevated fasting blood glucose level and all of the following features EXCEPT: a. proteinuria. b. dyslipidemia. c. prehypertension. d. central obesity.

proteinuria

Low levels of all of the following nutrients/minerals is associated with the development of hypertension EXCEPT: selenium. magnesium. potassium. calcium.

selenium

Major causes of secondary hypothyroidism and its result

stroke to hypothalamus/pituitary pituitary tumor postpartum pituitary necrosis (very rare) failure of the pituitary to synthesize adequate TSH

Describe the pathophysiology of increases RAAS activity that leads to HTN (include hormones and neurotransmitters).

the enzyme Renin is triggered by decreased BP → interacts with Angiotensinogen to form angiotensin 1 (AG1) → angiotensin-converting enzyme (ACE) triggers AG1 → AG 2 → vasoconstriction and interacts with aldosterone in the adrenal cortex → aldosterone increases Na+ → water reabsorption → increased BV/BP.

How do AGEs contribute to retinopathy and nephropathy?

vessel thickening and clotting of capillaries → retinal ischemia → retinopathy. Can also see retinal detachment and blindness (due to the 02 sensitivity of the rods/cones). Mechanisms are unknown, but will manifest with; intraglomerular HTN, basement membrane thickening, glomerulosclerosis → proteinuria/albuminuria → chronic renal failure and ESRD.