Final Exam Flashcards
Other Factors That Lead To Coagulation Defects (besides platelets)
Liver
Vitamin K Deficiency
Aspirin
Liver (Other Factors That Lead To Coagulation Defects)
Liver makes many coagulation factors
Vitamin K Deficiency (Other Factors That Lead To Coagulation Defects)
Vitamin K is needed for clotting factor synthesis
May occur in:
- newborn
- those treated with broad spectrum antibiotics
- liver/gall bladder disease - impaired fat absorption
Aspirin (Other Factors That Lead to Coagulation Defects)
Can cause impaired platelet aggregation (makes slippery)
Inhibits COX pathway
-and therefore the production of thromboxane AZ (which is needed for platelets to stick together; causes bleeding tendencies)
Portal Hypertension
Increased resistance in the hepatic portal circulatory route due to liver disease
- causes congestion in the veins
- mainly seen in cirrhosis (scar tissue - hard for venous blood to get through)
Danger of Portal Hypertension and Liver Disease
Esophageal Varicies Rupture
Rupture when you swallow
Varicies
Engorged, twisted veins
Hereditary Defects In Coagulation
von Willebrand Disease (vWD)
Hemophilia
von Willebrand Disease (vWD)
MOST COMMON hereditary defect
Lacking vWF produced by endothelial cells - needed for platelet adhesion
Hemophilia
Sex-linked recessive disorder (x-linked, therefore all daughters of hemophiliac men are carriers) in which an insufficient quantity of the factor is produced (~90% of cases) or it is defective (~10% of cases)
Varying degrees of severity depending on the amount of factor produced (causing bleeding problems)
(Defect in coagulation)
Coronary Artery Disease (CAD)
A disease in which blood flow to the myocardium is diminished due to narrowing of one or more of the coronary arteries
Risk Factor
A risk factor is a characteristic, symptom, or sign that is associated with development of the disease
CAD Risk Factors
Determined mainly by Framingham Study
- High blood cholesterol: > LDLs and < HDLs
- High blood pressure - hypertension (normal is UNDER 120/80)
- Cigarette smoking - damages the endothelium
- Obesity (waist circumference >40” for men and >35” for women)
- Lack of physical activity (sedentary lifestyle)
- Diabetes mellitus
- Family history (genetics)
- Sex (men at higher risk, and women after menopause)
- Age
- Others (homocystine - influenced by diet, increased levels = increased risk and C Reactive Protein - a marker of inflammation)
Etiology of CAD
- Atherosclerosis: LEADING CAUSE
2. Coronary Artery Vasospasm
Coronary Artery Vasospasm
A condition in which the smooth muscle in the arterial wall constricts and blocks blood flow
-Endothelial dysfunction? (>endothelium and <N.O.)
Atherosclerosis
Deposition of fatty plaque in the walls of the arteries
Pathogenesis/Atherosclerosis Mechanism:
Fatty Streaks -> Fibrous Plaques -> Complicated Lesion
Fatty Streaks
LDL’s and macrophages collect between endothelium and C.T.
Myointimal cells accumulate too.
Fibrous Plaques
Fibrous scar tissue forms around LDL’s and foam cells.
STABLE PLAQUE = intact endothelium overlying plaque
Complicated Lesion
Cells in plaques die and calcify.
If endothelium is damaged platelets stick forming overlying thrombus
Prone to ulceration, hemorrhage, and emboli.
This is UNSTABLE PLAQUE
Common Sites of Atherosclerosis
Areas of turbulent blood flow
Aorta and main branches
Symptoms may not occur until..
artery is 75% occluded
WHY?
- for a time, compensatory vasodilation via nitric oxide release tires to compensate for the narrowing
- eventually even a moderate increase in demand exceeds flow and ischemia results
- symtoms vary greatly from individual to individual
- with diabetics commonly experiencing NO symptoms
Atherosclerosis Outcomes
- Occluding vessels over time
- Occluding vessels suddenly via rupture or thrombosis
- Weakening vessel walls to the point on aneurysm
CAD Leads To:
- Angina
- Sudden Cardiac Death
- Myocardial Infarctions
- Conduction Disturbance
- CHF
Angina Pectoris
Symptomatic , paroxysmal chest pain due to transient (short-lived) myocardial ischemia.
Pain may radiate to the arms, chin, shoulder
3 Types of Angina
- Stable
- Varient
- Unstable
Stable Angina
Frequently occurs during activity.
Alleviated by rest
“Classic” angina
-usually follows physical exertion/stress = increase in myocardial demand
Associated with fixed obstructions in the coronary arteries
(stable plaques)
As HR increases, diastolic filling time is decreased = decreased flow through atherosclerotic coronary vessels, which leads to myocardial
Stable Angina - pain described as:
pressure, heaviness, tightness
Why is it associated with exertion?
-increased demand for blood, but not enough flow
Stable Angina - Treatment
Nitroglycerin - to vasodilate coronary vessels - brings relief to many patients
Warning! (stable angina)
If it lasts for more than 5-10 minutes or is not relieved by Nitro — NOT ANGINA
(Possibly a MI)
Prinzmetal’s or Varient Angina (vasospastic)
May occur when coronary arteries are stenotic or patent.
Occurs more often in women and may be due to vasospasm
- occurs most often between midnight and 6 am (when person is sleeping)
- exercise tolerant (not caused from exercise)
Mechanism unknown - endothelia dysfunction?
Unstable Angina
Occurs without trigger
Results from atherosclerotic plaque disruption and may lead to MI
Thrombi superimposed on plaque (dangerous)
- Associated with complicated plaque
- -no endothelium so thrombus develops (thrombus gets bigger and smaller, causing angina randomly)
Sudden Cardiac Death
Death Sudden
-loss of cardiac function (in someone who is PREVIOUSLY ASYMPTOMATIC)
Responsible for ~450,000 deaths per year in North America
Most Common Underlying Cause of Sudden Cardiac Death
CAD (with no warning signs)
Incident may be related to increased exertion, vasospasm, occlusion of coronary artery, thrombosis or arrhythmia, congenital malformation
Sudden cardiac death is first indication of CAD for many patients…. BUT
there is almost always at least SOME warning (in the weeks beforehand)
Myocardial Infarction
Cell death resulting from prolonged ischemia
(MI) Blood Flow Obstructed from:
- Thrombosis (80-90% of the time)
- Ulceration and hemorrhage from atherosclerotic plaque
- Prolonged vasospasm
- Sudden increase in oxygen demands of tissue
Right Coronary Artery (MI Artery Obstruction)
- inferior infarct
- posterior infarction
- involves posterior septum
- 30% of cases
Left Anterior Descending Artery
- anterior infarction
- apical (apex)
- artery of “sudden death”
- 50% of cases
Left Circumflex Artery
- lateral infarction
- can also be LAD
- 20% of cases
Characteristics/S&S of MI (listed)
- Pain and autonomic nervous system responses
- Weakness and other signs of imparied cardiac function
- ECG alterations
Pain and Autonomic Nervous System Responses (S&S of MI)
-Severe, crushing, suffocating pain (not relieved by rest or nitroglycerine), GI problems (nausea and vomiting), SOB, diaphoresis
Pain and sympathetic stimulation lead to:
-Tachycardia, anxiety, restlessness
NOTE: most common S&S for WOMEN are: weakness, SOB, fatigue
-1/3 of women die from MI
Weakness and Other Signs of Impaired Cardiac Function
Fatigue and weakness
Skin: pale, cool, and moist
Hypotension and shock
ECG Alterations:
ST segment elevation or depression
Q waves
Cell Death Causes
-Release of intracellular proteins and enzymes therefore fever and leukocytosis
(MI) Enzymes/Proteins Released Include
CPK: creatine kinase
CK-MB: cardiac specific
T: Troponin (now accepted as standard biomarker)
Myocardial Necrosis to Repair
1-2 days old:
- beginning acute inflammation
- marked by changes in the electrocardiogram and by a rise in the MB fraction of creatine kinase
1 to 2 weeks:
- many macrophages
- little collagenization
Necrotic tissue is repaired with scar tissue = fibrous CT
Diagnosis of MI
Requires two out of three components (history, EKG, and enzymes)
Post MI Complications
Determined by extent and location of injury
- Sudden death occurs in ~20% due to arrhythmias
- Heart failure. Blood becomes congested
- Cardiogenic shock - decreased CO below level required to perfuse tissue adequately
- Pericarditis
- Thromboemboli from stasis/inactivity
- Ventricular aneurysms: from scar tissues inelasticity
- Rupture of the heart
- Arrhythmias - most serious being ventricular fibrillation
Treatment of MI
- Coronary Artery Bypass Graft (CABG) of occluded artery
- Saphenous vein or internal thoracic artery
- LIMA preferred - Percutaneous Transluminal Coronary Angioplasty (PTCA) with stents
- open vessel and keep it from collapsing
- problem is restenosis
Diabetes Mellitus
Metabolic disorder of carbohydrate, protein, and lipid metabolism
Most common endocrine disorder
1-2% of US population
Diabetes Background Information
Affects 24 million in US and is under diagnosed!
Affects all age groups
Incidence is on the rise
Decreases life expectancy and can have a profound impact on quality of life
Normal Fasting Blood Glucose
Levels are <100 mg/dL
Glucose is the primary energy source for _______ and the only energy source for ______
- cell metabolism
- the brain
Blood glucose is controlled by the opposing effects of 2 hormones:
insulin and glucagon
secreted from the Islets of Langerhans (alpha and beta cells)
The antagonistic effects of tehse two hormones allow for careful regulation of this important plasma variable
Actions of Insulin:
- promote glucose uptake
- promote fat storage in form of FFAs
- prevent fat and glycogen breakdown
- prevent gluconeogenesis
- prevent protein breakdown
Blood Glucose Too High =
Pancreas secretes insulin
Blood Glucose Too Low =
Pancreas secretes glucagon
Notes on Insulin Receptors and GLUT
- Glucose cannot enter muscle cells without insulin
- In order for insulin to work, it must bind to insulin receptors on the C.M.
- Once bound, intracellular mechanisms are activated
- Which cause the cell to transport glucose transport proteins to the C.M.
- -the main glucose transporter in muscle is GLUT 4
- GLUT 4 binds to glucose
- Glucose is transported into the cell
- Glucose is used for metabolism
Diabetes Mellitus is a syndrome involving _____ and characterized by ____
- disordered metabolism
- chronic hyperglycemia
Hyperglycemia Stems from:
- Insulin deficiency
- Impaired release of insulin
- Inadequate or defective insulin receptors
- Production of inactive form of insulin
- Destruction of insulin
Type 1 DM
10% of cases
Absolute insulin deficiency
T cell mediated AUTOimmune attack
Type 2 DM
90% of cases
Combination insulin deficiency and/or resistance
Slow gradual progression and development of symptoms
Previously a disease of older individuals (>40)
-age is dropping as obesity becomes a childhood epidemic
Etiology of Type 1
Autoimmune destruction of beta cells in the islets of Langerhans
Why the beta cells self-antigens become altered and vulnerable to immune attack is unclear
Suspicions:
- Genetic - HLA’s
- Viral Exposure
NOTE: there are some people who develop Type 1 who show no evidence of immune dysfunction = idiopathic
Signs and Symptoms Emerge when
Most beta cells are destroyed, resulting in an absolute insulin deficiency
Pathogenesis of Type 1
- Hyperglycemia (may reach 1,200 mg/dL at extreme)
- Glycosuria as glucose is lost in the urine. Recall that glucose is removed from filtrate via carrier molecules that have a TM (transport maximum)
- osmotic diuresis occurs as the glucose exerts a substantial osmotic pressure and water is not reabsorbed from the renal tubules - Polyuria and
- Polydipsia result
Low insulin stimulates ____ and ____ to release more glucose into the blood
glycogenolysis
gluconeogenesis
But without insulin, the cells cannot take up glucose. Gluconeogenesis promotes the conversion of protein to glucose which results in fatigue, weakness, and muscle and weight loss
Lipid metabolism increases leading to ____ and production of _____.
hyperlipidemia
ketone bodies
This leads to metabolic acidosis called diabetic ketoacidosis
DKA (diabetic ketoacidosis) produces ___
nausea, vomiting, and brain toxicity
Ketones can be detected on the breath as ___
a sweet fruity odor.
An acidotic coma can result
Etiology Type 2
Strong genetic component (even stronger than Type 1) with multiple genes involved
Defective genes create two problems (diabetes type 2)
- Beta cell dysfunction - response is sluggish or muted
- insulin resistance - inability of cells to take up glucose
- glucose carriers are not cycled to the cell surface as readily
- defective cell use of the glucose that does enter the cells
Obesity (type 2 diabetes)
Over 80% of Type 2 are obese
-seem to have fewer insulin receptors
as obesity and genetics interact over time, type 2 emerges
Other strong etiological contributors
sedentary lifestyle - reduces the need for glucose uptake, so response is subnormal
Pathogenesis of Type 2
Genetic beta cell defect is operating before there are signs of the disease. This combines with insulin resistance to contribute to hyperglycemia
During the years as the disease progresses, the hyperglycemia acts as a strong insulin secretion stimulates promoting hyperinsulinemia that may create a fatiguing of the beta cells
Over time, the beta cells undergo apoptosis and a replaced with fibrous CT. Loss leads to the classic signs and symptoms of DM
Classic S&S of DM
Hyperglycemia
Glycosuria
Polyuria
Polydipsia
Other S&S may occur as acute or chronic complications arise
Complications of DM
Emergence of complications varies, depending on the length of time, severity, and compliance. Average onset is 15 years. Can be delayed by tight glucose control.
Theory (DM)
Abnormal glycoprotein (glycosolated protein) formation and attachment to basement membranes throughout the body to cause injury to target organs/structures
Within blood vessels, this leads to endothelial damage, atherosclerosis, and ischemia. Causes microvascular and macrovascular complications
Abnormal proteins also attach to hemoglobin = HbA1c
This leads to:
- Peripheral neuropathy
- Nephropathy
- Retinopathies
- Vascular Complications
- Infections
Peripheral Neuropathy
Ischemia and demyelination causes a decrease in impuls conduction (pins and needles type of nerve pain)
Nephropathy
Renal vascular complications (often the cause of death) impaired blood flow causes progressive destruction of nephrons and loss of renal function
Retinopathies
Diabetes is the leading cause of blindness in the US.
Capillaries rupture or form aneurysms that end to lead/burst. Scar tissue develops leading to retinal detachment, cataracts, and glaucoma
Vascular Complications
Accelerated rate of atherosclerosis causes
CAD
CVD
PVD (peripheral vascular disease) - resulting in intermittent claudication - pain in legs due to ischemia
Renal Stenosis
Ulceration, poor wound healing and gangrene
Infections
Poor circulation, poor immune function and high glucose concentration favor the growth of microbes
Management/Treatment of DM
Goal is tight glucose control (avoid wide fluctuations)
Type 1:
- maintain ideal weight
- work with dietician to adjust insulin therapy to lifestyle
- caloric intake based on body weight
Type 2:
- Early on, Type 2 can be controlled with diet, exercise, and weight loss
- weight loss increases numbers of insulin receptors thereby decreasing insulin resistance
- exercise will contribute to weight loss and increase in insulin receptors
- as the disease progresses, insulin therapy may be required to offset the loss of beta cells
Future of Diabetes?
Stem cell transplants
