THE SECOND MIDTERM Flashcards
1
Q
What are the nine major causes of death in order?
A
- Heart disease - 28% 2. Malignancies - 23% 3. Stroke 4. Emphysema 5. Accidents 6. Diabetes 7. Pneumonia 8. Alzheimer’s 9. Renal diseases - 1.7%
2
Q
Definition of hypertrophy and hyperplasia:
A
It is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. You are born with about all of the cardiac myocytes that you will get, but they can get bigger, this is hypertrophy.
3
Q
Definition of metaplasia:
A
It is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus. In simplistic terms, it is as if the original cells are not robust enough to withstand the new environment, and so they change into another type more suited to the new environment.
4
Q
Definition of dysplasia:
A
It is an ambiguous term used in pathology to refer to an abnormality of development or an epithelial anomaly of growth and differentiation. It is disordered hyperplasia without maturation.
5
Q
Definition of atrophy:
A
Cell shrinkage or loss, caused by lack of hormonal signals, loss of innervation, lack of use, loss of blood supply, starvation, individual cell death
6
Q
Definition of cachexia:
A
The formal definition of cachexia is the loss of body mass that cannot be reversed nutritionally: Even if the affected patient eats more calories, lean body mass will be lost, indicating a primary pathology is in place.
7
Q
At what percent of normal body weight is cachexia fatal?
A
Fatal at 68% of normal body weight
8
Q
What type of cell change is the uterine cervix, bowel in IBS, esophagus with Barrett’s?
A
Dysplasia
9
Q
What are the main eight causes of cell injury and death
A
- Trauma - force, heat, cold 2. Ischemia - inadequate circulation 3. Toxins & radiation 4. Infection 5. Inflammation 6. Genetic diseases 7. Nutritional problems 8. Tumors
10
Q
Which cells are most prone to injury?
A
Those that have a high metabolic activity and those that proliferate rapidly
11
Q
What are three examples of cells that have a high metabolic activity?
A
- Cardiac myocytes 2. Renal tubular cells 3. Hepatocytes
12
Q
What are three examples of cells that proliferate rapidly?
A
- Testicular germ cells 2. Intestinal epithelium 3. Hematopoietic cells
13
Q
What are the two degrees of cell injury and what are examples of each?
A
Reversible and Irreversible (cell death). An example of reversible is mild acute tubular necrosis of kidney, toxic livery injury, severe exercise. An example of irreversible is holes in cell membrane, long Ca++ influx, mitochondrial loss, and the two types of irreversible are necrosis and apoptosis.
14
Q
What happens during severe exercise to our cells in the body?
A
You get hypoxia because of loss of ATP, anaerobic glycolysis with acidosis, and cell swelling because loss of Na pump.
15
Q
Apoptosis involves inflammation. True or False?
A
False, it happens in normal cell turnover, viral infections, normal embryology, damaged cells.
16
Q
What are the early events of necrosis?
A
Cell membrane disruption, Ca++ signal, energy loss.
17
Q
Necrosis happens more often to individual cells rather than cell clusters. True or False?
A
False, it is the opposite
18
Q
Necrosis involves inflammation. True or False?
A
True, it incites acute inflammation from leakage of cell contents
19
Q
What is kariolysis?
A
It is the complete dissolution of the chromatin of a dying cell due to the enzymatic degradation by endonucleases. We get a digested, pale nucleus
20
Q
What is nuclear pyknosis?
A
Is when the nucleus becomes shriveled and dark.
21
Q
What is karyorrhexis?
A
It is when the nucleus becomes fragmented.
22
Q
What is coagulative necrosis?
A
Coagulative -See this in infarcts in any tissue (except brain) -Due to loss of blood -Gross: tissue is firm -Micro: Cell outlines are preserved (cells look ghostly), and everything looks red
23
Q
What is liquefactive necrosis?
A
Liquefactive -See this in infections and, for some unknown reason, in brain infarcts -Due to lots of neutrophils around releasing their toxic contents, “liquefying” the tissue -Gross: tissue is liquidy and creamy yellow (pus) -Micro: lots of neutrophils and cell debris
24
Q
What is caseous necrosis?
A
Caseous -See this in tuberculosis -Due to the body trying to wall off and kill the bug with macrophages -Gross: White, soft, cheesy-looking (“caseous”) material -Micro: fragmented cells and debris surrounded by a collar of lymphocytes and macrophages (granuloma)
25
What is fat necrosis?
Fat necrosis -See this in acute pancreatitis -Damaged cells release lipases, which split the triglyceride esters within fat cells -Gross: chalky, white areas from the combination of the newly-formed free fatty acids with calcium (saponification) -Micro: shadowy outlines of dead fat cells (see image above); sometimes there is a bluish cast from the calcium deposits, which are basophilic
26
What is gangrenous necrosis?
Gangrenous necrosis -See this when an entire limb loses blood supply and dies (usually the lower leg) -This isn’t really a different kind of necrosis, but people use the term clinically so it’s worth knowing about -Gross: skin looks black and dead; underlying tissue is in varying stages of decomposition -Micro: initially there is coagulative necrosis from the loss of blood supply (this stage is called “dry gangrene”); if bacterial infection is superimposed, there is liquefactive necrosis (this stage is called “wet gangrene”)
27
What are the six main abnormal storage products? And details about them?
1. Fatty change of liver (common with alcoholism, obesity, starvation, toxins. 2. Glycogen accumulation (in liver in diabetes, in glycogen storage disease, in certain tumors) 3. Lipid (lipid storage disease -Fabry's-Gaucher's, lysosomal accumulation of lipid, in vessels in atherosclerosis) 4. Brown storage (lipofuscin is degraded lipid in lysosomes, increases with age and free radical damage, bilirubin is a hemoglobin breakdown product, normally present in bile, increased with biliary obstruction & hepatocyte disorders, too much causes jaundice, Hemosiderin is an iron containing pigment that is increased with excessive iron absorption, you get bleeding into tissues) 5. Protein storage (alpha-1 antitrypsin deficiency and russell bodies in plasma cells are intracellular examples, whereas amyloid is an extracellular example and is a beta pleated sheet protein accumulation. 6. Calcification (you can get dystrophic or metastatic calcification (into damaged or normal tissue), an example of metastatic is disorder of calcium metabolism, renal failure, hyperparathyroidism)
28
What is the name for Coal Worker's lung?
Anthracosis, abormal storage products in lung
29
What is edema?
Too much extravascular fluid in tissues. Hormonal fluid retention, heart failure, and inflammation are common causes for edema. Dependent edema is when fluid accumulates in lower part of body. A common cause of pulmonary edema is heart failure.
30
What is effusion?
Too much fluid in body cavity, examples are ascites, excess fluid in peritoneal space, pleural effusion, and hydrocephalus, excess cerebrospinal fluid.
31
What is ascites?
Massive peritoneal space fluid in a liver failure patient.
32
Tumors often grow into veins and embolize. True or False?
False, they rarely do. But foreign material, amniotic fluid, and air can embolize and cause infarcts by blocking blood flow.
33
If left heart isn't doing its job, what would you get?
It would back up and it would cause pulmonary edema
34
If right heart isn't doing its job, what would you get?
It would back up in the veins and you would get edema throughout the whole body.
35
What are the three common causes of hypotension?
1. Hypovolemic (low blood volume, blood flows mainly to vital organs) 2. Cardiogenic (heart infarct or failure, arrhythmia, pulmonary emboli 3. Septic shock (overwhelming infection, vasodilation and high permeability, poor cardiac pumping, patient often febrile, flushed, chills, poor prognosis unless infection is rapidly controlled.
36
What is congestive heart failure?
It is when the cardiac output is insufficient for metabolic needs of the body. You can get systolic dysfunction, which is decreased myocardial contractility (heart pumps weakly), diastolic dysfunction, which is insufficient expansion (heart does not fill with blood between beats). And problems are accentuated by increased demand.
37
What are the body's five main methods to compensate for congestive heart failure?
1. Tachycardia 2. Frank-Starling (increased end diastolic volume results in increased stroke volume) 3. Myocardial hypertrophy 4. Increased catecholamine activity leading to positive ionotropic effect (they tell the myocytes to keep contracting the best you can), as well as renin-angiotensin-aldosterone system 5. Redistribution of blood flow
38
How does left-sided heart failure occur and what are the consequences?
It is caused by ischemic heart disease, hypertension, aortic and mitral valve disease, myocardial disease like cardiomyopathy. You get pulmonary edema and breathing problems, dyspnea (breathlessness), orthopnea (dyspnea while lying down due to vascular congestion and it develops within minutes), paroxysmal nocturnal dyspnea (extreme dyspnea, develops over a few hours, due to pulmonary edema from heart failure while lying down). You also get reduced perfusion to organs like kidneys, ending up with prerenal azotemia (high BUN with less high or normal creatinine) or ischemic tubular necrosis.
39
How does right-sided heart failure occur and what are the consequences?
Can be caused by right-sided heart disease or cor pulmonale (abnormal enlargement of right side), and can be a consequence of left-sided failure, or due to myocarditis, cardiomyopathy. You end up getting chronic passive congestion to the liver, congestive splenomegaly, congestion and hypoxia to the kidneys, peripheral edema and anasarca (extreme edema), pleural effusions, venous congestion and hypoxia, and ascites.
40
What are the main symptoms of a myocardial infarct?
Retrosternal chest pain, dyspnea, diaphoresis (sweating), nausea/vomiting, palpitations, anxiety, or can be asymptomatic or present as sudden death.
41
What is the diagnostic criteria for a myocardial infarct?
You need at least 2 of the following: -Ischemic type chest pain for more than 20 minutes -Acute EKG changes -Rising, then falling serum cardiac biomarkers (troponin, CK) -Documentation of an infarct at autopsy
42
What is a transmural infarct?
It is due to an anuerysm in the heart wall and it has full thickness, endocardium to epicardium. Usually involving left ventricle anterior and posterior free wall or septum with extension into right ventricle wall in 15-30% of cases. More severe than MI, correlates with ST segment elevation myocardial infarct on EKG.
43
What is a subendocardial infarct?
It is due to hypotension, global ischemia, and is multifocal or diffuse areas of necrosis confined to inner 1/3 to 1/2 of left ventricular wall. Infarct is not necessarily in distribution of one coronary artery. Correlates with Non-ST segment elevation myocardial infarct on EKG, less severe but still potentially lethal.
44
What are the main complications of myocardial infarcts, and which are most common?
Most to least common 1. Arrhythmias 2. Congestive heart failure and pulmonary edema 3. Pericarditis 4. Mural thrombosis 5. None 6. Cardiogenic shock 7. Rupture of ventricle or papillary muscle
45
In referring to valvular heart disease, what is stenosis?
A failure to open, prevents forward flow
46
In referring to valvular heart disease, what is regurgitation?
A failure to close, allows reverse flow
47
What are the main two causes of calcific aortic valve stenosis?
Post infective endocarditis or rheumatic fever. It is also common in congenital bicuspid valves or normal valves of elderly people.
48
What are the main causes of aortic regurgitation?
Postinflammatory scarring, syphilitic aortitis, ankylosing spondylitis, rheumatoid arthritis, Marfan's syndrome
49
What is a mitral valve prolapse, and who usually gets it?
It is excessively large leaflets in the mitral valve, long chordae tendineae, or myxomatous change within valve leaflets especially posterior leaflet. Could be hereditary or associated with Marfan's syndrome, happens with 2-3% of population, mostly women, susceptible to endocarditis and psychiatric disorders.
50
What are the systemic symptoms of rheumatic fever?
Polyarthritis of large joints, carditis, subcutaneous nodules, sydenham's chorea, used to be very common but due to antibiotic treatment for strep throat, not very common anymore.
51
Where does infective endocarditis usually take place in the heart?
Mitral valve and aortic valve - 25-35% of time Tricuspid valve, valve prosthesis, congenital defect - 10% of time. It consists of friable vegetations containing RBCs, fibrin, inflammatory cells and organisms.
52
What are the main causative agents of infective endoarditis?
Staph aureus, strep, pseudomonas, HACEK, polymicrobial. Fever and murmur are common, and mortality is as high as 70% if staphylococcal.
53
What re the main complications of infective endocarditis?
Cardiac complications, which are coronary artery emboli, abscesses, erosion of valve or chordae tenineae. Non-cardiac complications, which are septic emboli, immune complex diseases in vessels or kidneys.
54
What are the complications of artificial valves?
Thrombosis, can cause thromboembolism, anticoagulant related hemorrhage, increased risk of infective endocarditis, structural or biological deterioration, nonstructural dysfunction-tissue entrapment, paravalvular leaks, anemia, wears out valves and leaks.
55
What is an arrhythmia?
Palpitations, irregular heartbeat, premature atrial or ventricular contractions, the most common kind are normal EKG, infrequent, no other heart disease. Can have tachyarrhythmia, which is more serious.
56
What is syncope?
Fainting, due to hypotension or low cardiac output, arrhythmias happen to about 1/3 of patients with syncope, often serious, need EKG and evaluation. Presyncope if feeling lightheaded.
57
How do you differentiate a seizure from syncope?
Look for postictal changes with seizures, confusion for 2-10 minutes after seizures.
58
What are the usual cause of sudden cardiac death?
Arrhythmias, most often from coronary atherosclerosis, although infarct is not needed.
59
What is bradycardia?
Heart rate of less than 60 beats per minute
60
What is tachycardia?
Heart rate of more than 100 beats per minute
61
What can contribute to bradycardia?
Disturbances in impulse generation to the sinus node, impulse propagation from the sinus node to the atria, impulse propagation through the AV node/His-Purkinje system. Bradycardia due to abnormal impulse propagation is known as a conduction block.
62
What are the main causes of conduction disturbances?
Ischemic heart disease and cardiomyopathic scarring, degenerative changes in the conduction system, antiarrhythmic drugs, hyperkalemia, myocardial infection (lyme disease), trauma, congenital abnormality.
63
What is a first degree heart block?
It is a slow but reliable impulse propagation to ventricles, generally not symptomatic, no treatment.
64
What is a second degree heart block?
It is when impulse propagation to ventricles sometimes fails. You get irregular ventricular contractions, sometimes causes syncope, pacemaker sometimes needed.
65
What is a complete or third degree heart block?
No conduction of any atrial electrical impulses to the ventricles, ventricles resort to latent pacemakers, result is more P waves than QRS complexes, QRS complexes are regular as determined by latent pacemaker, no relationship between P and QRS complexes, and you get syncope and risk for sudden cardiac death.
66
What is an ectopic beat?
It is an increased rate of depolarization, at any site, to a rate faster than the sinus node which results in a premature depolarization. It is called ectopic because it originates from a site other than the sinus node.
67
What are the three main places where ectopic beats usually originate form?
1. The atria (APDs, atrial premature depolarization) 2. Specialized conduction system - usually the AV node or His bundle (Junctional premature depolarizations) 3. The ventricles (VPDs, ventricular premature depolarizations)
68
What can an ectopic focus that is firing rapidly or multiple ectopic foci collectively causing a fast rhythym end up causing?
Tachycardia and Tachy-arrhythmias
69
What is a re-entrant arrhythmia?
Normally, electrical waves stop propagating when they encounter unexcitable tissue, re-entry occurs when the wave form does not extinguish as it continues to find excitable tissue.
70
How does re-entrant tachycardia persist?
For re-entry tachycardia to persist, the leading edge of the electrical wave front must always meet excitable (repolarized) tissue that is ready to depolarization, if it meets refractory tissue, the wave front will be extinguished and re-entry will stop. Conduction delay within the re-entrant circuit is crucial in maintaining the re-entry as it creates an excitable gap between the head of the wave front and refractory tissue at its tail.
71
What is atrial fibrillation?
It is the most common sustained arrhythmia in adult clinical cardiology. Atrial flutter is different and involves very rapid atrial contractions, and can turn into atrial fibrillation. AF increases with age and often co-exists with other cardiovascular diseases like congestive heart failure, valvular heart disease, and hypertension. 10% of Americans older than 65 years old have AF. It is associated with electrical and structural changes of the atrium. You get electrical remodeling, meaning shorter atrial action potentials, loss of rate of adaptation to action potential duration, and loss of myocytes and replacement with collagen and fibroblasts. AF causes inefficient atrial contraction, which causes decrease in cardiac output, due to loss of atrial contribution to ventricular filling, and is also involved with a high risk of thrombosis and embolization.
72
What is ventricular fibrillation?
It is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. P waves are absent here, and can quickly lead to sudden cardiac arrest or death.
73
When does sudden cardiac arrest occur?
When there is an abrupt cessation of ventricular function due to rapid ventricular tachycardia or ventricular fibrillation. It is fatal 90% of the time.
74
Who is the population at risk of sudden cardiac arrest?
Patients with coronary artery disease, patients with heart failure, patients with inherited channelopathies causing ventricular arrhythmias.
75
How fast does brain damage and brain death occur within sudden cardiac arrest start?
Within 4-6 minutes, and it is reversible in most individuals if it is treated within minutes with CPR and defibrillator. A victim's chances of survival are reduced by 7-10% per minute without CPR and defibrillator.
76
What is the main cause of cardiovascular mortality?
Sudden cardiac arrest, it is due to fast ventricular tachycardia and ventricular fibrillation.
77
What is unique about atrial fibrillation and atrial flutter and their risk associations?
They are both associated with a thrombo-embolic risk, while other arrhythmias are typically not associated with this risk.
78
What is sudden cardiac arrest?
Cardiac arrest, also known as cardiopulmonary arrest or circulatory arrest, is a sudden stop in effective blood circulation due to the failure of the heart to contract effectively or at all. A cardiac arrest is different from (but may be caused by) a myocardial infarction, where blood flow to the muscle of the heart is impaired. It is different from congestive heart failure, where circulation is substandard, but the heart is still pumping sufficient blood to sustain life. Arrested blood circulation prevents delivery of oxygen and glucose to the body. Lack of oxygen and glucose to the brain causes loss of consciousness, which then results in abnormal or absent breathing. Brain injury is likely to happen if cardiac arrest goes untreated for more than five minutes. For the best chance of survival and neurological recovery immediate treatment is important. Cardiac arrest is a medical emergency that, in certain situations, is potentially reversible if treated early. Unexpected cardiac arrest can lead to death within minutes: this is called sudden cardiac death (SCD). The treatment for cardiac arrest is immediate defibrillation if a "shockable" rhythm is present, while cardiopulmonary resuscitation (CPR) is used to provide circulatory support and/or to induce a "shockable" rhythm. A number of heart conditions and non-heart-related events can cause cardiac arrest; the most common cause is coronary artery disease.
79
What is considered a hypertensive emergency or crisis?
Direct acute organ damage, often with a BP greater than 180/110. It causes severe vessel damage.
80
What is essential hypertension?
No obvious cause, very common, nearly 50 million in US, 95% of all hypertensive patients. Possible causes include increased sodium retention & intravascular volume, narrowing of arteries, high TPR lowers blood pressure in kidneys, kidneys sense lower pressure and signal to retain sodium to increase BP, vicious cycle.
81
What is secondary hypertension?
Uncommon, 5% of all hypertensive patients, possible causes include endocrine (steroid, pheochromocytoma), drugs, pregnancy, renal failure, sleep apnea, pain, stress.
82
What are the main hypertension-induced problems?
Accelerated atherosclerosis due to endothelial injury, myocardial infarcts, stroke, peripheral vascular disease, aneurysms, heart failure, renal failure, retinal and brain damage, hemorrhages.
83
Which side of the heart gets bigger when body has systemic hypertension?
Left side has to pump harder so it undergoes hypertrophy.
84
What happens to the kidneys with extreme hypertensive changes?
Arterionephrosclerosis, the kidneys become smaller and have a finely pitted surface, very common in black people.
85
What percent of US adults have hypercholesterolemia levels above 200 mg/dl? 240 mg/dl?
50% and 13%
86
What are the secondary causes of hyperlipidemia?
These are far more common than familial by the way, but they are diabetes, sedentary lifestyle, poor diet, obesity, heavy alcohol. Familial is primary hyperlipidemia and has to do with genetics.
87
What are the four major lipoprotein classes?
1. High density - HDL 2. Low density - LDL 3. Very low density - VLDL 4. Chylo-microns
88
Where do HDL's deliver lipids to?
They deliver lipids periphery to liver
89
Where do LDL's and VLDL's deliver lipids to?
They deliver lipids liver to periphery
90
Where do chylo-microns deliver lipids to?
They deliver lipids gut to liver
91
What kind of lipoproteins are apo-B associated with?
LDLs and VLDLs, the bad ones, lipids induce atherosclerosis, they leak into vessel intima, induce macrophage response/inflammation, the inflammatory response induces smooth muscle cells in intima, fibrosis, calcification, and an atheroma can rupture into lumen and cause a thrombus.
92
What is the leading cause of death in America, and what causes 80% of that?
Heart disease, and Atherosclerosis does. Atherosclerosis can also be main cause of stroke, main cause of peripheral vascular disease.
93
What is arteriosclerosis vs atherosclerosis?
Arteriosclerosis is the hardening of the arteries. Atherosclerosis is lipid deposits, plaques in arteries, and can cause arteriosclerosis.
94
What is the mechanism behind atherosclerosis?
Endothelial dysfunction (smoking, hypertension, diabetes, lipids, inflammation) then lipids deposit in vessel wall intima, then inflammation/foamy macrophages, which all can do 1 of 2 things, either go to intimal smooth muscle, cause fibrosis, cause fibroatheroma with stenosis, which can lead to angina, claudication, etc, or it can cause plaque ulcer or rupture, which can lead to thrombosis (ruptured or ulcerated plaques), which causes most infarcts and sudden death.
95
How does atherosclerosis cause stenosis and disease?
Resistance to flow is inversely proportional to diameter^4 (i.e. inversely proportional to cross sectional area^2). You must have 75% stenosis (decreased cross sectional area) to clinically impede flow. This increases resistance 16-fold. Slow stenosis causes stable angina while abrupt stenosis or occlusion can cause infarcts/sudden death and is associated with a thrombus or embolus. A rupture/erosion causes a complicated lesion, and is the most common cause of most infarcts.
96
Where does arteriosclerosis usually happen?
Aorta, coronary arteries, iliac/femoral/and politeal arteries, carotids/circle of willis arteries, kidney, and pulmonary arteries.
97
What are the consequences of atherosclerosis in the aorta?
Very common in the aorta, most often below the renal arteries, the aorta is usually never occluded complete, but damage to media can cause aneurysm, and can rupture. Abdominal Aortic Aneurysm risk factors include family history, smoking, hypertension, but lipids do not matter for AAA. Ulcerated plaques can embolize.
98
What are the consequences of atherosclerosis in coronary arteries?
It causes 80% of heart disease:angina, infarct, chronic ischemic heart disease. Common sites are proximal 2-3 cm of LAD and LCX, and entire length of right coronary artery. Ruptured plaque with thrombus and erosion on a plaque with thrombus is most common, and rarely a hematoma in the plaque will happen. But you can't predict well with an angiogram who is most at risk for an infarct.
99
What are the consequences of atherosclerosis in the peripheral arteries like iliac, femoral, and popliteal arteries?
Causes claudication (ache, pain, fatigue with exertion), then ulcers and ultimately gangrene.
100
What are the consequences of atherosclerosis in the carotid and circle of willis?
Erosions (not rupture) of a plaque is the more common cause of a thrombus here, and these are closely associated with hypertension, hypercoaguability, and old age, but less with hyperlipidemias and other risk factors.
101
What is a stroke?
Defined as an abrupt onset of focal or global neurological symptoms caused by ischemia or hemorrhage. Symptoms must continue for \>24 hours and are usually associated with permanent damage to brain tissue. If symptoms resolve within 24 hours, the episode is called a transient ischemic attack - TIA. Also called CVA, cerebrovascular accident, or brain ttack.
102
What is the most common cause of strokes?
Cerebral infarct, 60-80%. then intracerebral hemorrhage, 10-30%, then subarachnoid hemorrhage, 5-10%
103
What is Cor pulmonale?
It is enlargement and failure of the right ventricle due to pulmonary hypertension and RV hypertrophy.
104
What are the ten main risk factors associated with atherosclerosis?
1. Inreasing age (\>45 male, \>55 female) 2. Smoking (endothelial injury, increased coagulation and free radials) 3. Diabetes and metabolic syndrome 4. Hypertension (endothelial injury) 5. Dyslipidemia (promotes deposition in vessels) 6. Family history/genetics 7. Male or postmenopausal female (lack estrogenic protective effects like HDL) 8. Lifestyle factors (obesity, inactivity, poor diet) 9. Inflammatory markers (local or systemic inflammation) 10. Periodontal disease
105
What are the atherosclerosis main key points?
Exremely common cause of death. Due to endothelial damage, lipid deposits, inflammation, fibrosis/smooth muscle, and rupture or erosion causing thrombosis. Thrombosis (not stenosis) is the main cause of infarcts. Often happens in areas of only mild/moderate stenosis. Stenosis (not thrombosis) is the main cause of predictable pain with exertion, like angina and claudication (leg pain).
106
What percentage of heart disease deaths does Ischemic heart disease cause in US? (also known as coronary artery disease, or atherosclerotic heart disase)
Causes 70% of US heart disease-deaths and 30% of total mortality.
107
When we get severe stenosis in coronary arteries, in what layer of the vessels do most changes take place?
Tunica Intima
108
Why can slow stenosis be asymptomatic sometimes and not cause angina or claudication?
Because of good collateral circulation
109
What is the process of atherosclerosis?
Endothelial injury, then lipid deposits, then inflammation, then fibrosis, then calcification, and this is all mostly in the tunica intima. Then because of this we get slow stenosis which can cause angina and claudication, and then we can get a thrombus/disrupted plaque, where blood flow abruptly stops, we get a myocardial infarct, arrhythmia, sudden cardiac death, and gangrene.
110
What is an atheroma?
It is an accumulation of degenerative material in the tunica intima (inner layer) of artery walls. The material consists of (mostly) macrophage cells, or debris, containing lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. The accumulated material forms a swelling in the artery wall, which may intrude into the channel of the artery, narrowing it and restricting blood flow. Atheroma occurs in atherosclerosis, which is one of the three subtypes of arteriosclerosis.
111
What are the main three types of angina?
1. Stable angina 2. Variant angina 3. Unstable angina (most dangerous, prolonged pain)
112
What is stable angina?
Pain that feels like pressure for 2-5 minutes and associated with exertion. Relieved by rest or vasodilators (nitroglycerine). It is subendocardial ischemia, and you get a ST-segment depression. Usulaly due to fixed coronary stenosis.
113
What is variant or prinzmetal's angina?
It classically occurs at rest. Brief, like stable angina. Reversible spasm, ST-segment elevation (instead of depression with stable angina).
114
What is unstable angina?
New or worsening angina, prolonged pain or pain at rest. You get an ST-segment depression, and often due to acute plaque change. Most dangerous.
115
What is sudden cardiac death, how many people per year die because of it?
It is unexpected death within 1 hour of cardiac event, usually due to a high grade coronary stenosis, ventricular electrical instability, and arrhythmia. 300--400,000 people every year.
116
What are the four major classes of antihypertensives?
1. Diuretics (deplete sodium, reduce blood volume) 2. Sympathoplegics (reduce peripheral vascular resistance) 3. Direct vasodilators (relax vascular smooth muscle, dilating vessels) 4. Anti-angiotensin agents (inhibit action/production of angiotensin and thus reduce peripheral vascular resistance)
117
Mannitol
It is an osmotic agent. It draws free water out of tissues (including the brain) and into the intravascular space, and can transiently decrease cerebral edema (until excreted by the kidneys). Mannitol is freely filtered in the glomerulus, but cannot be reabsorbed. Thus, it remains in the lumen of the nephron and lowers osmotic pressure. Water then "follows" mannitol into the lumen due to the osmotic pressure.
118
Acetazolamide
It is a carbonic anhydrase inhibitor, which will decrease the reabsorption of NaCO3 in the end, because the proton pump isn't working because CA was blocked, so without that proton pump, less NaCO3 is reabsorbed, and more is secreted, and water will follow. Works in the primary convoluted tubule. It also changes the pH to make urine more basic because not as much acid is being secreted. This drug is used for treating glaucoma, epilepsy.
119
Furosemide
It is a loop diuretic. It inhibits the luminal Na/K/2Cl transporters in the thick ascending limb of the loop of Henle, thus reducing NaCL reabsorption and increasing its secretion. Can also cause hypokalemia, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions. Diuretics, especially furosemide, can also be used to treat heart failure. Does not have positive ionotropic effect, but you are getting fluid accumulation because heart is not working very well, which will cause problems to whole body so you use a potent diuretic like furosemide.
120
Bumetanide
It is a loop diuretic. It inhibits the luminal Na/K/2Cl transporters in the thick ascending limb of the loop of Henle, thus reducing NaCL reabsorption and increasing its secretion. Can also cause hypokalemia, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions.
121
Hydrochlorothiazide
It is a loop diuretic and it is a thiazide. It inhibits NaCl reabsorption from the luminal side of epithelial cells in the distal convoluted tubule by blocking the Na/Cl transporter. Can also cause **hypokalemia, and this is a problem because of cardiac arrhythmias**, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions.
122
Chlorthalidone
It is a loop diuretic and it is a thiazide. It inhibits NaCl reabsorption from the luminal side of epithelial cells in the distal convoluted tubule by blocking the Na/Cl transporter. Can also cause hypokalemia, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions.
123
Spironolactone
This drug is a potassium-sparing diuretic. Most diuretics cause us to lose potassium through urine, sometimes people who take those drugs will also be given a potassium-sparing drug to take with it. This drug prevents K secretion by antagonizing the effects of aldosterone in collecting tubules (via blockade of mineralocorticoid receptors).
124
Amiloride
This drug is a potassium-sparing diuretic. Most diuretics cause us to lose potassium through urine, sometimes people who take those drugs will also be given a potassium-sparing drug to take with it. This drug prevents K secretion by antagonizing effects of aldosterone in collecting tubules via Na influx through ion channels in the luminal membrane.
125
Clonidine
Is an alpha-2 agonist in the medulla that reduces sympathetic tone, resulting in decreased blood pressure. Remember that alpha-2 can be an autoreceptor. Dry mouth, sedation are common. Both effects are centrally mediated and dose-dependent.
126
Mecamylamine
Rarely used, but is a nicoticic neuronal receptor antagonist. It competitively blocks nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia. Causes excessive orthostatic hypotension and constipation, urinary retention, blurred vision, dry mouth, so it has sympathoplegic and parasympathoplegic effects.
127
Guanethidine
This is an adrenergic blocking agent, it inhibits the release of norepinephrine from sympathetic nerve endings by entering the nerve, then replacing norepinephrine, thus gradually depleting NE stores in the nerve ending. Side effects include orthostatic hypotension and diarrhea.
128
Atenolol
Beta-1 antagonist that is also used to lower blood pressure, angina, glaucoma. Effects include decreased HR and contractility, increased TPR because of beta-2 blockage in skeletal muscle (seems counterintuitive, what decreased HR is more important factor), decreased renin release, bronchial constriction, decreased glycogenolysis in response to hypoglycemia, decreased aqueous humor production.
129
Metoprolol
Beta-1 antagonist used to lower blood pressure, angina, glaucoma. Effects include decreased HR and contractility, increased TPR because of beta-2 blockage in skeletal muscle (seems counterintuitive, what decreased HR is more important factor), decreased renin release, bronchial constriction, decreased glycogenolysis in response to hypoglycemia, decreased aqueous humor production. Also used to treat heart failure.
130
Propranolol
Non-selective beta antagonist used to lower blood pressure, and also inhibits the stimulation of renin production by catecholamines (mediated by beta-1 receptors) and thus, it is likely that propranolol's effect is due in part to depression of the renin-angiotensin-aldosterone system. Effects include decreased HR and contractility, increased TPR because of beta-2 blockage in skeletal muscle (seems counterintuitive, what decreased HR is more important factor), decreased renin release, bronchial constriction, decreased glycogenolysis in response to hypoglycemia, decreased aqueous humor production.
131
Nadolol
Non-selective beta antagonist used to lower blood pressure, and also inhibits the stimulation of renin production by catecholamines (mediated by beta-1 receptors) and thus, it is likely that propranolol's effect is due in part to depression of the renin-angiotensin-aldosterone system.
132
Labetalol
This drug is a beta and alpha-1 antagonist used to treat high blood pressure, angina, glaucoma.
133
Carvedilol
This drug is a beta and alpha-1 antagonist used to treat high blood pressure, angina, open-angle glaucoma.
134
Prazosin
This drug is an alpha-1 antagonist. Causes vasodilation and thus decreased TPR and decreased BP. Used to treat hypertension, benign prostatic hypertrophy. Side effects include orthostatic hypotension, nasal congestion.
135
Terazosin
This drug is an alpha-1 antagonist. Causes vasodilation and thus decreased TPR and decreased BP. Used to treat hypertension, benign prostatic hypertrophy. Side effects include orthostatic hypotension, nasal congestion.
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Phentolamine
This drug is a non-selective alpha antagonist
137
Phenoxybenzamine
This drug is a non-selective alpha antagonist.
138
Tamsulosin
A adrenergic alpha blocker used to treat benign prostatic hypertrophy.
139
Hydralazine
This drug is a direct vasodilator that releases nitric oxide from the drug or from endothelium. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. Also used to treat heart failure.
140
Verapamil
This drug is a direct vasodilator that reduces calcium influx, is a calcium channel blocker. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. This drug is also used to treat angina by prevent Ca influx through L-type channels and blocking contraction of smooth and cardiac muscles while reducing O2 demand. Can cause cardiac depression, bradycardia, flushing. This drug is also considered a class IV anti-arrhythmia drug.
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Diltiazem
This drug is a direct vasodilator that reduces calcium influx, is a calcium channel blocker. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. This drug is also used to treat angina by prevent Ca influx through L-type channels and blocking contraction of smooth and cardiac muscles while reducing O2 demand. Can cause cardiac depression, bradycardia, flushing. This drug is also considered a class IV anti-arrhythmia drug.
142
Nifedipine
This drug is a direct vasodilator that reduces calcium influx, is a calcium channel blocker. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. This drug is also used to treat angina by prevent Ca influx through L-type channels and blocking contraction of smooth and cardiac muscles while reducing O2 demand. Can cause cardiac depression, bradycardia, flushing.
143
Minoxidil
This drug is a direct vasodilator that hyperpolarizes smooth muscle membrane through opening of potassium channels. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension.
144
Captopril
This drug is an ACE inhibitor (any drug that ends with pril, is usually an ACE inhibitor). It inhibits the converting enzyme (peptidyl dipeptidase) that hydrolyzes angiotensin I to angiotensin II, so you can't get increased blood pressure through the ACE pathway. This also allows bradykinin to stay active (because ACE turns it off usually), which is a potent vasodilator that stimulates the release of nitric oxide and prostaglandins. You also get major hyperkalemia with these drugs. Also used to treat heart failure.
145
Losartan
This drug is an angiotensin II inhibitor (ACE helps convert angiotensin I to angiotensin II). It decreases peripheral vascular resistance, but has no effect on bradykinin (a potent vasodilator) metabolism and is therefore a more selective blocker of angiotensin effects than ACE inhibitors.
146
What are the mediators that actually cause angina pectoris?
It is due to ischemia-related metabolites like glucose and other factors.
147
What are the best ways to treat angina?
Vasodilation, decreased O2 consumption via beta blockers and calcium channel blockers, nitrates and nitrites (which are metabolized to nitric oxide), which increase smooth muscle relaxation.
148
Nitroglycerin
Allows nitric oxide to float around in the body causing vasodilation to the arteries of the heart, treating angina and chest pain, it also decreases myocardial O2 consumption. They have long-lasting patches for 8 hours, and it is volatile, needs to be stored in closed glass container. Side effects include orthostatic hypotension, tachycardia (reflex), throbbing headache. Tolerance develops rapidly.
149
Amyl nitrate
Used to treat angina, and this is used for someone who can only breath in the drug instead of swallow. Ampule is crushed and fumes inhaled, it is short acting.
150
Why can atenolol be more helpful in treating angina than propranolol?
Because atenolol is a selective blocker, you have a smaller risk for bronchospasms. And beta blockers are used to treat angina prophylactically.
151
What habit has been shown to lower HDL values?
Cigarette smoking
152
What is primary hypercholesterolemia?
Also called familial, and it is an autosomal dominant gene. LDL ranges from 260-500 mg/dl, but triglycerides are usually normal. Coronary disease is often premature, and you have defects in LDL receptors.
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How do you treat familial hypercholesterolemia?
You don't use drugs, you improve diet first, if no coronary involvement, include complex carbohydrates and fiber, avoid alcohol if VLDL elevated.
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Lovastatin
This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle. This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle.
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Atorvastatin
This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle.
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Simvastatin
This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle.
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Fenobrate
This drug, used to treat hypercholesterolemia, is a fibrate that increases oxidation of fatty acids in liver and muscles (causes lipolysis). It reduces VLDL and has modest effect on LDL, and a moderate increase in HDL while reducing triglycerides. It's main side effects are GI symptoms.
158
Niacin
Nicotinic Acid, it helps decrease triglyceride and LDL, used to treat hypercholesterolemia, always causes flushing though, and tolerance develops.
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Cholesteramine
This drug is used to treat hypercholesterolemia and it is a bile acid-binding agent. It reduces absorption of bile acids and metabolites. It all goes to the stool though so you end up getting constipation and bloating.
160
Ezetimibe
This drug is used to treat hypercholesterolemia and it is an inhibitor of intestinal sterol absorption. It inhibits intestinal absorption of cholesterol and reduces LDL. If you have a genetic problem though, this won't do much good. This is great if you have a diet problem.
161
If you are a younger patient and have heart failure, is it more likely a systolic or diastolic problem?
Systolic, reduced contractility and reduced ejection. Diastolic likelihood increases with age and we get a reduced filling to the ventricles.
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Digitalis
This drug is a positive ionotropic drug, and digitalis is a genus plant name that provides cardiac glycosides such as digoxin. It increases intracellular Ca and cardiac contractility, only temporarily though. It helps treat heart failure. It increases blood ejection. It is not just selective for cardiac calcium channels so its side effects are that it affects all excitable tissues. Can cause premature depolarizations and ectopic beats.
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Milrinone
This drug is a Bipyridine that works like digitalis, helps treat heart failure. It increases contractility and Ca flux. But unlike digitalis, this is synthetic and not naturally-occurring.
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Dobutamine
This drug is a beta-1 agonist that is used to treat heart failure. Can cause arrhythmias.
165
What percentage of patients with a history of myocardial infarctions have arrhythmias?
80%, because of all of the scar tissue there.
166
What are the four classes of drugs used to treat heart arrhythmias?
Class I - Sodium channel blockade Class II - Block sympathetic autonomic effects on heart (beta blocker = Propanolol) Class III - Prolong refractory period Class IV - Ca channel blockade (Verapamil and Diltiazem)
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Procainamide
Class I anti-arrhythmic drug. It blocks sodium channels. Involved with cocaine, and local anesthetics, so if you inject it into an artery, can cause problems. Usually not first choice drug because it can precipitate new arrhythmias. It slows action potential conduction.
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Quinidine
Class I anti-arrhythmic drug. Has similar actions to procainamide. It blocks sodium channels. Involved with cocaine, and local anesthetics, so if you inject it into an artery, can cause problems. Usually not first choice drug because it can precipitate new arrhythmias. It slows action potential conduction.
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Lidocaine
Class I anti-arrhythmic drug. Effective against infarct-related arrhythmias. Is the first choice for ventricular arrhythmias, which are the worst kind!
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Amiodarone
Class III anti-arrhythmic drug. It helps prolong the refractory period, treats ventricular arrhythmias and atrial fibrillation. A side effect is pulmonary fibrosis.
171
Which two organisms that cause pneumonia in the immunocompromised often demonstrate blood vessel invasions?
Aspergillus and Mucormycosis. Aspergillus histo has acute angled branching/septa.
172
What greater risk number do smokers have of developing lung cancer?
10-55X, squamous cell and small cell most closely tied to smoking.
173
What is the definition of Atelectasis? What can cause it?
Collapse, caused by inadequate expansion of airspaces. Gives rise to hypoxia, can be caused by airway obstruction, compression, pleural effusion, pneumothorax, aspiration, pleural fibrosis.
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What is dyspnea?
Acute shortness of breathe, difficulty breathing.
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What is ARDS?
Acute Respiratory Distress Syndrome - and it is progression of acute injury and damage from activated neutrophils.
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What is COPD?
Chronic Obstructive Pulmonary Disease. Includes emphysema, chronic bronchitis, asthma, bronchiectasis, and the main cause is cigarette smoke.
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What is emphysema?
It is destruction of alveolar walls leading to permanent enlargement of airspaces. Caused by smoking, alpha-1 antitrypsin deficiency (imbalance of proteases and antiproteases), air pollution. You get a barrel chest with hyperinflation, low Forced Extrctory Volume.
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What is alpha-1-antitrypsin?
-it is rare, but their liver doesn’t produce antitrypsin, which helps control trypsin, which destroys particles in lungs that would do bad, but we need to be able to control trypsin.
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What does smoking do to alpha-1-antitrypsin?
It inhibits it, so trypsin goes uncontrolled and destroys particles in lungs and good tissue in lungs.
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What is the difference between centrilobular emphysema and panacinar emphysema?
Cintrolobular is smoking-related, and panacinar is alpha-1-antitrypsin related.
181
What are the requirements for chronic bronchitis?
Persistent productive cough for 3 months in 2 consecutive years, and it is caused by smoking, air pollution and has hypersecretion of mucus by airways and infections are often secondarily present. If the mucus glands get expanded and reach greater than 40$ to the epithelium, than it suggests chronic bronchitis - Reid index.
182
What is bronchiectasis?
Results from obstruction of the bronchi and persistent necrotizing infections. You get destruction of elastin and muscles in bronchial walls-congenital expression often caused by cystic fibrosis. You get persistent productive cough, and the infection which causes the suppurative pneumonia is usually caused by TB, Staph, Klebsiella (Alcoholics).
183
What is asthma?
It is a reactive airway disease and narrowing of airways-hyperreactivity: hyperinflated lungs, thick mucus plugs in airways, smooth muscle hypertrophy • Types: • Atopic- childhood onset often with allergic rhinitis, type I hypersensitiviy response. • Non-atopic- non-immune, occupational exposures, like aspirin or viral infections.
184
What are signs of restrictive lung diseases?
Reduced lung compliance, more effort required to expand lungs, leading to dyspnea, "ground-glass" infiltrates, fibrosis is common.
185
What are fibrosing lung diseases?
Associated with collagen vascular diseases such as rheumatoid arthritis-restrictive lung disease: stiff lung and hard to expand lungs. Usual Interstitial Pneumonitis is UIP and is idiopathic pulmonary fibrosis and this type has the worst prognosis. RB-ILD and DIP is common in smokers, but good prognosis if they quit.
186
What are the types and what can cause occupational lung diseases?
They are restrictive, and are mineral dust induced lung injury and fibrosis (restrictive), e.g., mineral dust-induced, silicosis [inhalation of crysalline silica by sandlblasters and miners], asbestosis [mesothelioma].
187
What is sarcoidosis?
It is also a restrictive lung disease, believed to be driven by anormally stimulated CD4+ helper T cells. Abnormal connective tissue and reduced elastic properties; multi-organ involvement.
188
What is a pulmonary embolus?
Can cause sudden death if in pulmonary artery. Origin from deep veins in legs. Cause: prolonged bed rest, surgery, congestive heart failure. Small emboli can cause pulmonary hypertension.
189
What causes pulmonary hypertension and what are the consequences?
Causes: heart disease, recurrent thromboemboli, and it can cause cor pulmonale- right ventricular failure.
190
What are the three main types of lung diseases and a summary of each?
1. Restrictive: caused by fibrosis or chest wall abnormalities; gas exchange impaired; difficulty inhaling and expanding lungs 2. Vascular: gas exchange impaired by obstruction or hemorrhage; may be abrupt or insidious 3. Obstruction: blocked airways; gas exchange through septal walls not impaired; unable to exhale
191
What are the main organisms that cause Community Acquired Pneumonia?
S. pneumoniae, H, influenzae, S. aureus.
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What are the main organisms that cause Community Acquired Atypical Pneumonia ("walking pneumonia")?
Mycoplasma pneumoniae, viruses like influenza
193
What are the main organisms that cause Hospital Acquired Pneumonia?
Enterbocteriaceae, Pseudomonas, S. aureus
194
What lobe is usually involved with aspiration pneumonia?
Right lower lobe - caustic gastric contents
195
What are the characteristics of Tuberculosis?
D. Tuberculosis-caused by mycobacterium tuberculosis 1. Usually lungs but can affect other organs 2. Flourishes in crowded, impoverished areas 3. Non-contagious during long periods of dormancy 4. Problems with multidrug antibiotic resistance 5. Forms necrotizing granulomas
196
What are the common organisms that cause pulmonary fungal infections?
Histoplasma (Ohio River Valley), Coccidiodes (Valley fever, Utah), Blastomycoses
197
What causes pneumonia in the immunocompromised?
Pneumonia in immunocompromised (e.g., AIDS) -Can be caused by micro-organisms including from normal flora -CMV (cytomegalo virus-common infection) causes ‘owl’s eye’ histology -Pneumocystis jiroveci is also an opportunistic fungus
198
What is the leading cause of cancer deaths in the world for both men and women?
Lung tumors. 95% of primary lung cancers are carcinomas.
199
What are the subtypes of lung carcinoma?
- Non-small cell carcinomas include adenocarcinoma and squamous cell carcinoma. (adeno and squamous cell [contains keratin] types most common) - Large cell neuroendocrine carcinoma - Small cell carcinoma
200
In which population is asthma the greatest?
In children, especially women.
201
In terms of pulmonary pharmacology, what are relievers?
They are rapid bronchodilators (Beta-2 agonists), used at minimum dose and frequency. They are short-acting, for less severe cases. Drugs include albuterol and salmaterol.
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Albuterol
Fast acting reliever, the only true "rescue" reliever, acts within 15 minutes and is effective for 4-6 hours. directly relax airway smooth muscle and bronchodilate.
203
Salmeterol
Pulmonary reliever, slower onset, longer-acting reliever than albuterol, effective 12 or more hours. directly relax airway smooth muscle and bronchodilate.
204
What kind of drugs are considered asthma controllers?
]Take regularly for long-term stable control-often more side effects Inhaled: corticosteroids/drug of choice for moderate to severe asthma -often combine with β 2 agonists, e.g., fluticasone + salmeterol (Advair Diskus) -chronic management, not for rescue
205
Fluticasone
Inhaled steroid for controlled asthma, prevents transcription of inflammatory mediators in the nucleus, resulting in a decrease in inflammation. Side effects: nose bleeds, sores in nose, mouth, tongue that don’t heal, oropharyngeal candidiasis (thrush), interfere with growth in children.
206
What are two antifungal treatments that help with candidiasis associated with using steroids for asthma?
1. Fluconazole 2. Clotrimazole
207
What class does methylxanthine drugs fall into?
Add-on controllers for Asthma.
208
Theophylline
Is a type of methylxanthine drug used as an add-on controller for asthma, it is a phosphodiesterase inhibitor and increases cAMP and relaxes airway smooth muscle. Available as tablet or inhaler through tea. Monotherapy for mild asthma. Combine with corticosteroids to reduce steroid doses and side effects. Also helps relax diaphragmatic fatigue in COPD. Toxicity: nausea, headache and anxiety. Requires plasma level monitoring.
209
What do antimuscarinics do for Asthma?
During an asthma attack, ACh is released from the vagus nerve. Antimuscarinics like ipatroprium bromide reverses the contraction of airway smooth muscles and production of mucus caused in response to this vagal activity.
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Ipatroprium Bromide
Is an antimuscarinic used to treat Asthma and specifically bronchospasms, related to Tiotropium Bromide-(Spriva)-which is not approved for asthma, but is approved to treat COPD) –reverses contraction of smooth muscle from vagal activity-usually backup for beta 2 agonists-sometimes combine antimuscarinics with β2 agonists (eg, albuterol). Reversible blockade of acetylcholine by antimuscarinics prevents the release of IP3 and prevents the inhibition of ACh at postganglionic muscarinic receptors. • Side effect of dry mouth • Used as an inhalant for bronchospasms
211
What do leukotriene modifiers do for Asthma?
Use is for prophylaxis and chronic treatment-for patients who have trouble with inhaled therapies (e.g., nasal bleeding)-can take orally-especially good for aspirin-induced asthma. Montelukast is an example drug. Mechanism: block leukotriene-binding to receptor.
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Montelukast
Selective leukotriene receptor antagonist (leukotrienes are associated with the pathophysiology of asthma (airway edema, smooth muscle contraction)). Used for prophylaxis and chronic treatment of asthma. So this blocks the synthesis of leukotrienes, this would be good for patients who comply poorly to inhaled therapies.
213
Cromolyn
This drug is considered a mast cell stabilizer, is used to treat asthma, inhibits release of inflammatory mediators such as histamine (mast cell stabilizer). Prophylactic use often before exercise and allergen exposure—no rescue action (i.e., not a replacement for albuterol).
214
Omalizumab
Drug used to treat asthma, considered a monoclonal antibody. Inhibits IgE binding to mast cells-very expensive, only for severe non-responsive asthma. This is reserved for patients with chronic severe asthma inadequately controlled by high dose corticosteroid plus long-acting beta-2 agonist combination treatment who have been shown to have IgE mediated sensitivity.
215
What are the dental relevant points regarding asthma?
• Asthmatics tend to be mouth breathers—dry mouth • Asthma inhalers irritate muscosa of mouth, especially back of roof of mouth • Remember stress (such as being in a dentist office), can precipitate an asthma attack-be prepared to address • Make sure asthmatics bring inhalers to appoint: avoid asthma attacks • Steroid use can cause oral sores and candida infections (thrush)
216
What are the main causes of COPD?
• Long smoking hx, or exposure to environmental irritants • Airflow limitations-due to progressive, irreversible airway remodeling • Not fully reversible in contrast to asthma which can be at least partially reversible
217
What are the main treatments for COPD?
• Longer acting bronchodilators such as Tiotropium Bromide (Spireva) • Longer acting beta 2 agonists such as Salmeterol • Theophylline with glucocorticoids (glucocorticoids alone not very effective) • Typically responses not as good as with asthma
218
How are influenza viruses classified and what are the main treatments?
They are classified by their core proteins, A, B, or C, species of origin, and geographic site of isolation. Most antiviral drugs for influenza have activity for influenza A. • Oseltamivir (Tamiflu)-prevents separation of virus particle from cell receptors, stopping viral spread—earlier treatment essential (can decrease the duration of flu 1-2 days)-works against type A and B flus.
219
Amantadine
An antiviral and a weak anti-Parkinson drug, effective against influenza A but not influenza B.
220
NRTs
Nictoine Replacement Therapies. Gum or transdermal patch, action of NRTs derive from the slow absorption of nicotine which delays and limits binding at alpha-4-beta-2 receptors in the CNS to reduce cravings and the pleasurable feelings of smoking.
221
Bupropion
Is a tetracyclic antidepressant that also helps people quit smoking. Smoking cessation name is Zyban.
222
What are the main causes of chronic renal disease?
Diabetes, Hypertension (-aterionephrosclerosis caused by hypertension or diabetes -hyaline thickening of arterioles), Chronic Glomerulonephritis (can be acute or chronic
223
Why do diabetics get nephritic syndrome because of worsening proteinuria?
They get nephrotic syndrome because they run out of the plasma proteins that they should have in their blood because of the proteinuria, and they start getting edema because of this.
224
What are the three main congenital kidney diseases or disorders, and their characteristics?
1. Single or fused kidneys (horseshoe) 2. Renal dysplasia (multiple cysts, cartilage, urinary tract dysfunction) 3. Adult polycystic kidneys (genetic (dominant), renal insuffiency, linked to intracranial aneurysms, other organs also have cysts, enlarged kidneys)
225
When does urinary obstruction cause severe, irreversible renal damage if it is a complete obstruction? Partial?
3 weeks, 3 months
226
What is the pathology of a urinary obstruction?
Hydronephrosis and dilated ureter. If distal to bladder can get dilated bladder with a thickening of the bladder wall. Can be caused by or create stones.
227
What does hydronephrosis cause?
Inability to concentrate urine (first defect), reflux and or lack of effective peristalsis cause pyelonephritis, complete loss of function - late complication.
228
What are symptoms of a urinary obstruction?
Anuria, polyuria, bladder distention, sometimes asymptomatic.
229
What are the symptoms of urinary stones?
Renal Colic, hematuria, pyelonephritis, or asymptomatic
230
What are the four main types of kidney stones?
1. Calcium oxalate (75%) 2. Magnesium ammonium phosphate (struvite, triple phosphate, 15% stones, alkaline urine) 3. Uric acid stones (5%), half are gout associated 4. Cystine stones (5%), defective tubular transport of cystine
231
What percentage of chronic renal failure does pyelonephritis cause?
10-20%
232
What is pyonephritis?
Severe pyelonephritis of entire kidney, uncommon, seen with obstruction
233
What is pyelonephritis?
Due to retrograde spread from cystitis or hematogenous spread, commonly seen with urinary obstruction, stenosis, can cause flank pain, fever, or asymptomatic, it is more severe in diabetics and with obstruction, can cause scarring.
234
Which adult renal tumors have a good prognosis?
Adenomas (histologically identical to papillary renal cell carcinoma, but less than 0.5 cm). Oncocytomas (generally have bland round nuclei with abundant eosinophilic cytoplasm). If you see mitochondria, think oncocytoma.
235
What causes 80-90% of all renal malignancies?
Renal cell carcinoma
236
In what population is renal cell carcinoma most popular?
Male, \>40, smoker, analgesic users, obesity
237
What are the symptoms of renal cell carcinoma?
Often clinically silent until large, painless hematuria, dull flank pain, fever, fatigue. Most likely metastasized to lungs or bones.
238
What are the two main cell types of renal cell carcinoma?
1. Papillary (If you see a bunch of macrophages, think papillary RCC) 2. Clear cell (abundant glycogen or lipid), and you see a lot of vascular background with RBC's in clear cell RCC.
239
What is Wilms tumor?
It is a nephroblastoma, a renal tumor found in children, and most common in first 3 years. It is the most common congenital tumor.
240
What is bacterial cystitis and what does it cause?
It is pyuria, dysuria, positive culture, and you get edema and neutrophils in mucosa.
241
What are contributing factors of bacterial cystitis?
Stones, cather, other foreign objects, reflux, short female urethra, obstructing lesions, diverticula.
242
What is schistosomiasis?
-infection from snails -leading cause of squamous cell carcinoma in bladder, found in urinary tract -primarily from Middle East -shitosomoiasis eggs deposited in bladder -causes obstruction, hydronephrosis, and malignant tumors
243
What are the characteristics of urothelial carcinoma?
• Most often in males \>50 years old • Associated with smoking, carcinogens (e.g., dyes, paint etc.) • Most common urothelial malignancy - Associated with Lynch Syndrome (HNPCC), they get colon cancer, urinary cancer, and upper tract infections.
244
What is the most common bladder malignancy in children?
Rhabdomyosarcoma
245
What usually causes prostatitis?
Often caused by bacteria, like cystitis, often seen with BPH and recurrent UTI's. And prostatitis causes enlarged and tender prostate, which can cause obstruction.
246
What does a prostatic massage reveal?
leukocytes
247
What are the main features of Benign Prostatic Hyperplasia?
• Very common in older men; 95% \> 75 years old • Serious sequelae less common • Cause not well known; perhaps has to do with androgens or even estrogens • Urinary obstruction is common-bladder can’t empty completely • 10% require surgery to relieve
248
Besides skin cancer, what is the most common malignancy in older men?
Prostatic adenocarcinoma, present in 60% of men greater than 80 years old. • Most often detected by rectal exams • Many are small and not clinically significant • Most metastasize to bone and occasionally to regional lymph nodes • However, can be deadly in some patients, especially in younger men - Serum PSA test (prostate specific antigen)
249
What are the characteristics of the serum PSA testing?
PSA (prostate specific antigen)-only associated with prostate tissue • \>4-6 mg/ml is abnormal (usually higher with age) • Rapidly increasing PSA means high risk for cancer • The more PSA bound to alpha-1-antichymotrypsin, the greater the risk of cancer (should be free in plasma) - PSA is also elevated in BPH and cancer
250
What is the treatment for prostatic adenocarcinoma?
• Prostatectomy (affects bladder function) • Radiation • Hormonal: block androgen receptors-affects male functions • Chemotherapy or bisphosphonate
251
A fetus has severe oligohydramnios and bilateral enlarged kidneys by ultrasound. At birth, there is severe pulmonary hypoplasia, resulting in nearly immediate death. The kidneys are large, but have the normal renal shape. This baby is likely to have: A. Autosomal dominant polycystic renal disease. B. Autosomal recessive polycystic renal disease. C. Renal dysplasia.
B
252
A 56-yearold man has hypertension and has developed slowly progressive renal failure, and his kidneys are 25 cm long (twice normal) and are deformed by innumerable large round cysts. Intermittently, he has had renal pain and hematuria. He is likely to have: A. Autosomal dominant polycystic renal disease. B. Autosomal recessive polycystic renal disease. C. Renal dysplasia.A
A
253
An adult who died of unrelated causes is found to have one small kidney (the other kidney, while slightly enlarged, is essentially normal). The small kidney has several cysts in it, some loose mesenchymal tissue, and cartilage. This patient has: A. Autosomal dominant polycystic renal disease. B. Autosomal recessive polycystic renal disease. C. Renal dysplasia.
C
254
A 31-year-old otherwise-healthy man presents with severe renal colic, with intermittent mild gross hematuria. He takes megadose vitamin C supplements. Abdominal films show a ureteral calculus. The stone is passed in the urine, and is analyzed chemically. What is the most likely composition? A. Urate. B. Cystine. C. Calcium oxalate. D. Struvite.
C
255
A 43-year-old woman with recurrent cystitis (Proteus has been cultured) has developed a panful renal stone. It is large, and involved an entire renal pelvis. What is the most likely composition? A. Urate. B. Cystine. C. Calcium oxalate. D. Struvite.
D
256
A 68-year-old man with urinary hesitancy and slow urinary stream, often has to get up twice a night to urinate. He presents to a urologist, and is found to have a moderately enlarged but not hard prostate. PSA is 4.2. Free PSA is 9%. The urologist decides to do a transrectal biopsy. What in this history is most concerning for a prostatic adenocarcinoma, which prompted the urologist to do the biopsy? A. His high PSA. B. His low free PSA. C. His large but not hard prostate. D. His urinary obstructive symptoms.
B
257
68-year-old male smoker with 9 cm diameter renal mass. He presented with dull flank pain, low grade fever, and polycythemia. What is it?
D - Renal Cell Carcinoma
258
73-year-old male smoker with intermittent hematuria and a small tan papillary bladder mass. Histologically, there are small papillary structures but the papillae are coated by benign-appearing urothelial cells. Urine cytology is negative. What is it?
Transitional Cell Papilloma
259
34-year-old renal transplant patient with large left kidney. It is yellow and has no areas of necrosis. Histologically, it is composed of foamy macrophages containing abundant bacteria. No Michaelis-Guttman bodies are seen. What is it?
Xanthogranulomatous pyelonephritis
260
21⁄2-year-old boy with large renal mass. It is composed of small cells with scanty cytoplasm. Focally, primitive glomeruli and tubules are formed by the tumor cells. What is it?
Wilms tumor
261
Cellular polypoid bladder tumor in 6-year-old girl. What is it?
Rhabdomyosarcoma
262
71-year-old former chemical plant worker who presents with painless intermittent hematuria. Cystoscopy shows a flat red lesion in the bladder, but no papillary structures or invasive mass. Urine cytology is compatible with carcinoma. What is it?
Transitional cell carcinoma in situ
263
Newborn with large renal mass composed of benign- appearing spindled cells. What is it?
Mesoblastic nephroma
264
What are the main causes of chronic renal disease?
Diabetes, hypertension, chronic glomerulonephritis
265
How do you treat small kidney stones (
• Drink considerable water • Dietary changes • OTC analgesics (ibuprofen, Naprosyn) • Tamsusolin (Flomax)—relaxes ureter muscle (often have spasm due to irritation of the stone)
266
How do you treat larger kidney stones (\>cm)?
• Lithotripsy (shock wave treatment)-break up stones • Surgical removal • Opioid analgesics for pain
267
What are the details surrounding the four most common types of kidney stones and how are they usually treated?
a. Calcium/oxylate: excess calcium and oxalate in urine (~80% of stones) -men more likely than women Alkalinize urine (stop drinking carbonated soft drinks) b. Struvite (~10% of stones)-magnesium ammonium phosphate crystals-often associated with urinary infections- only type where treatment is to acidify urine. -more common in females (the only type) c. Uric acid- excess waste, uric acid, in urine mineralizes into stones when urine is too acidic-often associated with gout -more common in men, must decrease uric acid production and alkanize urine pH d. Cysteine - excess cystine production causes hypercystinuria and deposition when urine is too acidic. Must dissolve cystine, thus alkanize urine and increase water consumption to flush kidneys.
268
Hydrochlorothiazide
A thiazide diuretic, very effetive in the DCT of nephron at reducing calcium in the urine and preventing calcium kidney stones.
269
Sodium Bicarbonate
Alkanizes urine, which decreases the amount of uric acid and cystine deposition from the urine. Recommended for uric acid and cystine stones, may also benefit calcium stones, but contraindicated for struvite stones, so don't give this to women with struvite crystals.
270
Penicillamine
Chelating agent that binds to cystine and improves its solubility in patients with cystine stones.
271
TMP-SMX
Used with patients with struvite (infection) stones, preventing or controlling UTI with antibiotics to prevent the recurrence of struvite stones. Also used for UTI's, -side effects include: photosensitivity, Stevens-Johnson syndrome- but usually the preferred treatment
272
Allopurinol
Reduces the amount of uric acid produced in patients with uric acid stones, also used for gout.
273
Acetohydroxamic Acid (AHA)
Used for kidney stones, is an irreversible inhibitor of bacterial urease, which will prevent formation and slow growth of struvite crystals, but has many side effects like increasing risk of phlebitis, deep venous thrombosis, and hemolytic anemia.
274
What are the organisms typically involved with UTIs?
E. coli, then Staph and Klebsiella.
275
Ciprofloxacin
Used for UTI's, is a 3rd generation fluoroquinolone, side effects include seizures.
276
Amoxicillin + Clavulonic Acid
Used for UTI's, is a beta-lactam, but resistant bacteria can be a problem.
277
What does Hemodialysis do?
It removes waste and excess water from blood through diffusion (waste removal) and ultrafiltration (fluid removal) and restores proper electrolyte balance, but does not correct kidney's endocrine functions like producing EPO.
278
What are the drugs commonly administered to patients on dialysis?
1. Atenolol (beta-1 selective antagonist) reduces hypertension and lowers heart rate. 2. Captopril (ACE inhibitor) reduces hypertension. 3. Heparin - anticoagulant which prevents the formation of clots in blood passing through the dialysis machine. 4. Furosemide - A loop diuretic used before to reduce fluid retention and amount of fluid that has to be removed during treatment. 5. Prophylactic antibiotics - prevent infection. Kidney disease patients or on dialysis have higher incidence of periodontal disease and are at greater risk of infections because of weakened immune systems.
279
What are the characteristics behind prophylactic antibiotics for dental procedures?
• Use for procedures associated with bleeding • Typically administer 30-60 min prior to procedure • Recommended: -amoxicillin or cefazolin preferred -clindamycin
280
What is primary and secondary hemostasis?
Primary involves platelets, • Typically initiated by injury • Adherence to subendothelium by interacting with von Willebrand factor - Secrete contents of granules • Aggregate with other platelets and form surface for coagulation cascade - Provide a procoagulant surface for the coagulation cascade Secondary involves the coagulation cascade-fibrin formation • Coagulation cascade (factors mostly made from liver) • Cascade of activating enzymatic conversions • Fibrin and platelet aggregates form stable clot a. Factors II, VII, IX and X are vitamin K-dependent-necessary for calcium binding sites activating coagulation cascade b. For final step thrombin catalyzes fibrinogen (soluble) to fibrin (insoluble) [note: thrombin acts at other levels of the cascade]. Fibrin cross-links form under the influence of Factor XIII
281
What are the features of platelets?
• Anucleated • Lifespan ~10 days • Circulating platelets do not adhere-during stasis, adhesion occurs
282
What are the natural anticoagulants and what do they do?
Protein C, protein S, and antithrombin. They inactivate activated coagulation factors and prevent growth of existing clot.
283
What is fibrinolysis?
It is mediated by plasmin and it breaks down fibrin clot and creates fibrin degradation products such as d-dimer.
284
What are the basic tests used to evaluate hemostasis?
• Platelet count (part of CBC-complete blood count) Coagulation cascade: • Prothrombin time-PT (12-15 seconds). Extrinsic and common pathways through factor VII • Partial thromboplastin time-PTT. Measures intrinsic and common pathways and includes factors XII, XI, X, VIII • Fibrinolysis • Prolonged coagulation tests may be due to deficiency or inhibitor of a coagulation factor
285
What is thrombosis?
The pathologic counterpart of hemostasis and also involves vessels, platelets, and the coagulation cascade.
286
What is Virchow's triad?
1. Endothelial injury 2. Abnormal blood flow (stasis, turbulence) 3. Hypercoagulability of blood (acquired or inherited factors) -These are things that can cause pathological clotting
287
What are some of the main acquired hypercoagulable states?
• Surgery/trauma • Limb immobilization • Bedridden • Long-distance air travel • Pregnancy • Advancing age • Oral contraceptives
288
What are some of the inherited coagulable states?
• Some aspect of cascade abnormal • Factor V Leiden-single nucleotide point mutation in coagulation factor V. Interferes with an anticoagulant factor, thus increasing formation of fibrin and becoming “prothrombic.” The mutation makes factor V resistant to cleavage and inactivation by activated protein C.
289
What is DIC and what is the test used to diagnose it?
Disseminated Intravascular Coagulation, activation of clotting should be limited to site of an injury, and this is a massive systemic intrasvascular activation of coagulation. You get elevated D-Dimer with this, which is a type of fibrin degradation product.
290
What three things are associated with bleeding disorders?
1. Abnormal vessels 2. Decreased platelets or platelet dysfunction 3. Abnormal coagulation factors
291
What is platelet-type bleeding and what causes it?
Mucocutaneous bleeding pattern from like skin and mucous membranes, petechiae, ecchymoses, epistaxis, GI bleeding are examples. Causes include vascular abnormalities, thrombocytopenia, qualitative platelet dysfunction, von Willebrand disease (interferes with von Willebrand factor preventing clot from adhering to endothelium and clot formation).
292
What is thrombocytopenia?
Decreased platelet count. Normal platelet count is 150,000 to 450,000 per microliter. It is quantitative. • Platelet counts
293
What can cause thrombocytopenia?
• Decreased bone marrow production • Hemodilution due to multiple transfusions • Immune reaction due to platelet autoantibodies directed at platelet surface proteins
294
What are some differences between inherited and acquired abnormalities in coagulation factors?
Inherited usually affect a single coagulation factor, Von-Willebrand disease (associated with factor VIII-get increased bleeding, hemophilia A and B. ), Hemophilia A (factor VIII) and B (factor IX - Christmas Disease): Have prolonged PTT and normal PT and platelet count: severe hemorrhaging internally/organs and soft tissue or into joints Acquired usually affect multiple coagulation factors, liver disease, vitamin K deficiency, DIC
295
What is a CBC?
A. CBC (complete blood count)—automated hematological evaluation—includes red and white blood cells and platelets
296
What are the factors that may affect CBC parameters?
• Iron deficiency • Medications • Alcohol • Infections • Gender • Pregnancy
297
What is a WBC?
The total white blood cell count (WBC, leukocyte count) includes all circulating nucleated hematopoietic cells with the exception of nucleated red blood cells (NRBCs). The WBC is of great importance in the diagnosis and management of patients with hematologic and infectious diseases.
298
What are the normal percentages and numbers for a WBC?
Normal WBC (3500-10,000 cells/microliter) differential: Neutrophils- 1800-6700 (55%) Eosinophils-0-570 (3%) Lymphocytes- 1400-3900 (35%) Monocytes 6% Basophils 0.5% •Note: pay attention to both total and percent
299
What is leukocytosis and what can cause it?
Leukocytosis- WBC\> 10,000 (a) Causes: • Chronic infection or inflammation • Exercise (can cause decreased margination • Some leukemias
300
What does MCV stand for?
Mean Corpuscular Volume = size of RBC
301
What is microcytic anemia and what causes it?
Microcytic (too few cells) • Iron deficiency (most often caused by hemorrhaging)-often has glossitis • Lead poisoning
302
What is the most common nutritional deficiency in the world?
Iron Deficiency Anemia, usually due to bleeding too much.
303
Where is iron primarily absorbed?
In the duodenum
304
What is macrocytic anemia and what causes it?
Macrocytic (too many cells) • Liver disease • Drugs • Vitamin B12 or folate deficiency-often includes neurological findings (paresthesia, weakness,dementia) (These two are megaloblastic anemia)
305
What do lymphomas and leukemias have in common?
They are both clonal expansions of white blood cells at certain developmental stages.
306
What is leukemia?
Systemically distributed neoplasms of white cells.
307
What are lymphomas?
They are solid tumors of the hematopoietic system, neoplasms of lymphoid origin, typically causing lymphadenopathy.
308
What are the different types of leukemia?
Acute vs. Chronic, and Lymphoblastic vs. Myeloid. Acute means blastic phase, early on, if you have 20% blast, then you can call it lymphoblastic acute leukemia.
309
What is the definition of acute myeloid or lymphoid leukemia?
• No evidence of maturation in blood or marrow • \>20% blast (immature) cells • Can have skin and gum infiltration
310
A 62 year old female presented with anemia and fever. Peripheral blood examination identified 35% myeloid blasts. This patient is diagnosed with A) chronic lymphoid leukemia B) acute lymphoblastic leukemia C) acute myeloid leukemia D) chronic myeloid leukemia
C
311
What are the two main types of lymphoma?
• Non-Hodgkin lymphoma (indolent to very aggressive: survival is years to weeks depending on type). Two examples are follicular lymphoma and diffuse large B cell lymphoma • Hodgkin lymphoma (all types-curable in most)
312
What are the lab values for total cholesterol?
\>200 mg/dL desirable 200-239 mg/dL borderline high \>240 mg/dL high
313
What are the lab values for LDL's?
189 very high
314
What are the lab values for triglycerides?
Triglicerides: 200 high
315
What are the lab values for HDL's (scavenger receptors)?
Scavenger receptors—HDL
316
What are the main drugs used to treat hypercholesterolemia?
Statins -inhibitors of HMG-CoA reductase-rate controlling step for synthesis of LDL-typically the most effective at lowering LDL up to 50-60% a. Drugs: -Lovastatin (been around a long time) -Rosuvastatin (Crestor \>$5 billion/yr sales) -Atorvastatin (Lipitor)
317
Although rare, what are some of the side effects associated with statins?
rare: elevate blood sugar, cognitive problems, muscle weakness, G.I irritation
318
What are the other less popular drugs used to treat hypercholesterolemia?
a. Niacin—side effects include annoying vasodilation and flushing of face b. Fibrates: e.g., gemfibrozil c. Bile acid binding resins such as cholestyramine d. Ezetimibe-inhibits intestinal absorption of cholesterol
319
What is the dental relevance of high LDL?
Won’t directly affect most dental procedures, but is suggestive that there may be cardiovascular disease present that will have an impact such as hypertension, potential MI or stroke, and artherosclerosis. Check for these other issues carefully.
320
What are the characteristics associated with the intrinsic pathway dealing with clotting through fibrin mechanisms?
1. Intrinsic pathway • Contact factors through factor XIa to Xa-this is measured by PTT (partial thromboplastin time) • Normal PTT is 25-35 seconds • Sensitive to heparin as an anticlotting agent • Side effects: hemorrhage, allergic reactions, osteoporosis and bone fractures • Heparin typically used in hospital setting
321
What are the characteristics associated with the extrinsic pathway dealing with clotting through fibrin mechanisms?
• Extrinsic factors pathway (i.e. from damaged tissue)-works through factor VIIa and leads to Xa and is measured by PT (Prothrombin time)/INR (international normalized ratio) • Normal PT is 11-13.5 seconds • Normal INR is 0.8-1.1 • Sensitive to warfarin (Coumadin) or -side effects: hemorrhage, numbness, pain, headache, dizziness -oral warfarin is prescribed for out patient
322
Dabigatran
Is an alternative drug for warfarin, has fewer side effects and is more popular than heparin or warfarin, it affects PTT sensitive pathway, but has unique mechanisms that makes it distinct from heparin and warfarin, used on out patient basis.
323
What is the definition of alcohol use disorder (AUD)?
AUDs are medical conditions that doctors diagnose when a patients drinking causes distress or harm.
324
What is the definition of binge drinking?
NIAAA defines binge drinking as a pattern of drinking that brings blood alcohol concentration (BAC) levels to 0.08 g/dL. This usually occurs after 4 drinks for women and 5 drinks for men—in about 2 hours.
325
What are the main reasons why individuals use, abuse, or become alcoholics?
Self medication, anxiety, depression, altered mental state, increased dopamine reward, genetics (50%, the other 50% is environment)
326
What is the basic pharmacology of alcohol?
Ethanol, small molecule, gets everywhere in the body, depressant, barbiturate-like.
327
What is alcohol's MOA?
It alters several receptors and cellular functions, including GABA-A receptors, Kir3/GIRK channels, adenosine reuptake (through the equilibrative nucleoside transporter, ENT1), glycine receptor, NMDA receptor, and 5-HT3 receptor. It also disrupts lipid membranes.
328
What are the pharmacokinetics behind alcohol?
It exhibits passive diffusion, gets everywhere, food slows its absorption, it is distributed everywhere, even through placental barrier and breast milk. it exhibits zero order kinetics, meaning constant rate, and independent of original concentration.
329
What is disulfiram?
-Disulfiram acts as a deterrant and when people drink it they feel awful so it tries to keep individuals from consuming large amounts. -Asians can turn red when they drink, they don’t have as much aldehyde dehydrogenase
330
At what Blood-Alcohol Concentration can alcohol be lethal?
0.4% is lethal, or greater than 400 mg/dL
331
What is the order in which alcohol affects the following various brain structures? Cerebellum Cerebral Cortex Hypothalamus and pituitary gland Limbic system Medulla
Cerebral Cortex Limbic system Cerebellum Hypothalamus and pituitary gland Medulla
332
What does alcohol do to the heart? Liver? Kidneys? GI?
-Their faces get flushed because it is a vasodilator -Low doses of alcohol can have some benefit, it can increase your HDL cholesterol -High doses can make you more likely to have high hypertension, more arrythmias, more coronary artery disease -Can cause liver cirrhosis -Can serve as a diuretic, decreasing ADH -Can increase GI acid secretion
333
What does alcohol due to our immune systems?
Suppresses both innate (white blood cells, cytokines that trigger inflammatory response) and adaptive (T- lymphocytes, B-cells) immune system
334
What are the main adverse effects from alcohol consumption?
Cancer -Increased risk in mouth, esophagus, increase GI cancer, increase liver cancer Malnourishment - Worse if you smoke, Vitamin deficiencies Fetal Alcohol Syndrome - facial abnormalities, impaired cognition, joints/bone problems Hang-Over --Headache, Nausea, Vomiting, Dehydrated
335
What are some symptoms that Alcoholics get when they try and withdraw?
Anxiety, insomnia, temor, nausea, palpitations, anorexia, seizures and hallucinations within first 1-4 days, delirium tremens (tachycardia, hypertension, fever, diaphoresis, delirium, agitation).
336
What are the most common drug interactions involving alcohol?
-The most common pharmacokinetic alcohol-drug interactions stem from alcohol-induced increases of drug- metabolizing enzymes. -Prolonged intake without damage to the liver can enhance the metabolic biotransformation of other drugs (i.e., induction of hepatic cytochrome P450 enzymes is particularly important with regard to acetaminophen, as it increases risk of hepatotoxicity as a result of conversion of acetaminophen to reactive hepatotoxic metabolites.) -Acute alcohol use can inhibit metabolism of other drugs because of decreased enzyme activity or decreased liver blood flow (i.e., phenothiazines, tricyclic antidepressants, and sedative-hypnotic drugs). -Additive/synergistic CNS depression if combined with other CNS depressants, particularly sedative-hypnotics -Potentiation of vasodilators and oral hypoglycemic agents (can also cause flushing)
337
Disulfiram
Used to treat Alcoholism. Inhibits ALDH (aldehyde dehydrogenase) with resulting ↑ acetaldehyde after drinking. Abstinence is reinforced to avoid the resulting adverse reaction.
338
Naltrexone
Used to treat Alcoholism. μ opioid receptor antagonist; felt to ↓ drinking through ↓ feelings of reward with alcohol and/or ↓ craving.
339
Acamprosate
Used to treat Alcoholism. Weak antagonist of NMDA receptors, activator of GABAA receptors; may ↓ mild protracted abstinence syndromes with ↓ feelings of a "need" for alcohol.
340
Where is the thyroid gland derived from?
Endodermal thickening in floor of pharynx.
341
Where are two main abnormal sites of ectopic thyroid?
Intralingual thyroid and lingual thyroid tissue.
342
What is the physiology of the thyroid gland, how is it regulated?
Pituitary secretion of TSH in response to low level of thyroid hormone with feedback inhibition. Hypothalamic TRH stimulates the release of TSH. Hypothalamic TRH stimulates release of TSH. Probably allows adaptation to starvation.
343
Are thyroid diseases strongly female or male predominant?
Female
344
What does excessive activation of the thyroid cause?
Causes hypermetabolic state causing protein catabolism and enhanced sympathetic nervous system activity.
345
What are the clinical findings of hyperthyroidism?
• Nervousness • Hot and sweating • Weight loss • Muscle weakness/tremor • Palpitations/tachycardia • “thyroid storm” (know symptoms)
346
What are the symptoms of a "thyroid storm?"
Fever, congestive heart failure, coma.
347
What is the lab diagnosis of hyperthyroidism?
Elevated free T4 or T3. Low TSH. Presence of serum TSI (immunoglobulins) is diagnostic of Graves disease.
348
What causes 90% of hyperthyroidism cases?
Graves Disease, found in 2% of adult females. The other cases are from toxic multinodular goiter (plummer's disease).
349
What causes Graves disease?
Autoimmune-antibodies function as agonists to thyroid-related receptors-causing excessive thyroid receptor activation. T-cell related autoimmune reaction
350
What are the findings and symptoms of Graves Disease?
Find elevated Ab to TSH receptor. Thyroid gland has a diffuse enlargement (2-3 times normal size). Symptoms: • Hyperthyroidism • Exophthalmos (protrusion of eyeballs), 1/3 of the cases
351
What are the clinical findings of hypothyroidism?
• Hypometabolic state (result of reduced thyroid activity) • In children, cretinism with reduced mental and physical development • Wide set eyes • Thick, dry and cool skin (cold intolerant) • Sluggish • Enlarged thyroid • Low temperature • Dry coarse skin and hair • Sluggish • Cold intolerance • Modest weight gain
352
What is the physiology of hypothyroidism?
Decreased free T4. • Increased TSH if cause is “primary” hypothyroidism. [Most cases] • TSH is normal or low with “secondary” hypothyroidism due to lack of pituitary function detected by decrease in other pituitary hormones or a TRH stimulation test. [Rare] • Since nearly all cases are primary, high TSH is a good screening test for hypothyroidism.
353
What is Hashimoto's Thyroiditis?
• Autoimmune; usually females --antithyroid peroxidase Ab present • May start as hyperthyroidism followed by permanent hypothyroidism • Thyroid enlarges- then atrophies over years • Most often in females • Radiation may cause • Most common cause of thyroid deficiency • High TSH, low free T3 and T4.
354
What is Subacute Granulomatous Thyroiditis?
• Viral cause (e.g., flu virus) • Painful • Usually self-limited and surgery not advised
355
What are the characteristics of a goiter?
• Most common lesion of the thyroid-usually a thyroid enlargement • Rarely associated with hypothyroidism • Not a cancer • Usually associate with deficiency of iodine • Diagnosed with fine needle aspiration (versus biopsy) to determine if have large follicles filled with colloid and relatively few cells • Can be confused with thyroid neoplasm—usually very cellular and little colloid
356
Most thyroid neoplasms are cancerous. True or False?
False, they are usually benign, nodular goiters.
357
What is the primary test for hypothyroidism?
TSH levels
358
What is the most common thyroid neoplasm?
Follicular Adenoma
359
Thyroid carcinomas are typically high risk, and have high metastatic rates. True or False?
False. Low risk, and low metatastasis. All papillary thyroid neoplasms are called malignant, but most are low risk. 10-year survival \>95%.
360
What is the function of the parathyroid gland?
• Secrete parathyroid hormone (PTH) regulated by free calcium in blood-reverse relationship (low calcium increases PTH) • PTH activates osteoclasts and bone resorption and increases serum calcium; also increases tubular reabsorption of calcium, activates vitamin D and increases GI absorption • Usually 4 glands close to thyroid poles
361
What does PTH act on and on what tissue cells does it act on?
PTH acts by binding a transmembrane receptor and activating cells in bone, GI tract, and kidney.
362
What is the main cause of hypercalcemia?
Hyperparathyroidism
363
What are the characteristics of primary hyperparathyroidism?
• A very common endocrine disorder; usually an adenoma (80% of time) • Symptoms: osteoporosis (fractures), constipation, nonspecific weakness, anorexia, stones, peptic ulcers, depression, or even coma. Bones, stones, groans, and moans. • Arrhythmias (1) Treatments usually surgical (2) Metastasis and carcinomas are rare
364
What are the characteristics of secondary hyperparathyroidism?
• Intestinal malabsorption of vitamin D or calcium • Chronic reduction of serum of Ca++ usually a consequence of chronic renal failure Stimulates PTH secretion, causes hyperplasia
365
What are the lab findings of hyperparathyroidism?
Elevated ionized serum calcium • Elevated or high normal PTH – PTH and PTHrP can be distinguished – Differentiates primary hyperparathyroidism from paraneoplastic syndrome – Increased urinary Ca+ and phosphate • Hypophosphatemia
366
What are the characteristics of hypoparathyroidism?
Very uncommon. Most often accidental removal at thyroid surgery, congenital absence of all glands. Symptoms: hypocalcemia, anxiety, depression, decreases PTH, tetany, dental changes in children (poor enamel, brittle teeth, missing teeth).
367
Where does the anterior pituitary arise from?
Adenohypophysis. Arises from evagination of roof of mouth (Rathke's Pouch).
368
Where does the posterior pituitary come from?
Neurohypophysis. Buds from the hypothalamus, with axons.
369
How does the pituitary gland secrete?
1. Brain’s endocrine gland, secretes through blood-brain barrier either: • Anterior-portal circulation from hypothalamus (sends “releasing” factors) • Posterior-axons go into systemic circulation
370
What are the six main hormones released from the hypothalamus to the anterior pituitary?
1. TRH 2. CRH 3. GNRH 4. GHRH 5. GIH 6. Dopamine
371
Which hormones from the hypothalamus act on which hormones from the anterior pituitary?
1. TRH - TSH 2. CRH - ACTH 3. GNRH - FSH, LH 4. GHRH - GH 5. GIH 6. Dopamine And Prolactin by itself.
372
What is the end target for the hormones from the anterior pituitary?
1. TRH - TSH - Thyroid, T4 2. CRH - ACTH - Adrenal Cortex, Cortisol 3. GNRH - FSH, LH - Reproductive tissues 4. GHRH - GH - Liver, IGF-1 5. GIH 6. Dopamine And Prolactin is released from the anterior pituitary and is for lactation.
373
What are the two hormones secreted from the posterior pituitary?
The posterior pituitary receives axons of nerves from hypothalamus, where ADH and oxytocin are produced. ADH (for water retention) & oxytocin (for nursing) are stored and released from neurohypophysis into systemic circulation, avoiding blood-brain barrier.
374
What is ACTH?
Controlled by hypothalamic CRH secretion. Controls the secretion of cortisol in adrenal cortex. Stress increases ACTH. Normal ACTH secretion has a diurnal variation; high in the early morning and low in late evening.
375
What is Growth Hormone?
GHRH sUmulates GH release GIH (somatostaUn) inhibits GH release GH has anabolic effect - promotes collagen & protein synthesis Growth effects of GH are mostly due to sUmulaUng somatomedins (esp. IGF-1) GH is insulin antagonist; GH secreUon is sUmulated by hypoglycemia and blocked by hyperglycemia
376
What is Prolactin?
Prolactin secretion is normally inhibited by dopamine from the hypothalamus. Prolactin increases during pregnancy, and stimulates milk production. Blocking dopamine signalling (tumor, portal vascular problem) increases PRL secretion.
377
What are FSH and LH?
FSH stimulates ovarian follicle growth, estrogen production. FSH plus testosterone promotes spermatogenesis. LH surge or “spike” induces ovulation. LH stimulates testosterone production in testicular Leydig cells; testosterone inhibits LH secretion.
378
What is TSH?
TRH stimulates TSH release; T3 and T4 inhibit TSH release TSH regulates: Biosynthesis, storage, & release of thyroid hormones. Size & cellularity of thyroid.
379
What is ADH and Oxytocin?
ADH is released due to: increased serum osmolality, decreased blood volume, decreased blood pressure. ADH causes renal water reabsorption. Oxytocin is released with suckling the breast by the infant and leads to uterine smooth muscle and breast myoepithelial cell contraction.
380
What is the most common problem of the pituitary?
Pituitary adenomas
381
What are the four common kinds of pituitary adenoma?
1. Prolactinoma (32%, galactorrhea, mass effects) 2. Growth Hormone (20%, acromegaly, gigantism) 3. Null cell / unclassified (30%, mass effects, can make clinically trivial amounts of FSH/LH) 4. Corticotroph (14%, Cushing disease)
382
At what age are pituitary adenomas most common? And what can they do to eyesight?
• Most common in 40-70 year olds • Can damage optic nerve and sight
383
What is the most common cause of hypopituitarism?
• Most common cause are nonsecretory pituitary adenomas
384
What are the main symptoms of anterior pituitary insufficiencies?
• Loss of sex characteristics-sterility • Retard growth in children • Hypothyroidism
385
What are the main symptoms of posterior pituitary insufficiencies?
• Diabetes insipidus –no glucose or insulin involved • Polydipsia (thirst) • Inappropriate ADH secretion from pituitary • Consequences : alters kidney function-volume (water) expansion, hyponatremia (low blood sodium levels) and hemodilution • Causes: metastasized carcinoma, CNS infection But problems can correct with administration of ADH.
386
What does the adrenal cortex make?
Mineralcorticoids, glucocorticoids and sex steroids
387
What does the adrenal medulla make?
Makes and releases catecholamines (epinephrine and norepinephrine)
388
What are the clinical features of primary acute adrenal cortical insufficiency?
• Weakness • Nausea • Hyponatremia, hyperkalemia • Hypotension • Skin pigmentation (get increase of MSH with the ACTH) • May cause ‘adrenal crisis’- a sudden requirement for increased steroid, which is not available; e.g., ‘Waterhouse-Friderichson syndrome’ caused by hemorrhaging into the adrenal cortex caused by sepsis from meningococcal infection
389
What is another name for primary chronic adrenocortical insufficiency? What is the cause and symptoms?
Addison's Disease. • Cause: autoimmune • More common in white women • 65% of adrenal insufficiency cases • Adrenals reduced • Increased infection ACTH is increased Caused by infections such as TB
390
What are the clinical features of secondary adrenocortical insufficiency?
Due to hypothalamic or pituitary problem Features; • No hyperpigmentation • Aldosterone usually normal • usually due to exogenous treatment with steroids and their abrupt discontinuation An ACTH challenge test will result in increased cortisol levels
391
What is the leading cause of hypercortisolism?
Cushing Disease.
392
What are the main features and symptoms of Cushing Disease?
• Leading cause of hypercortisolism: women 5X more likely • Adrenal hyperplasia • ACTH low, cortisol high • Adrenals act autonomously • Symptoms: moon face, osteoporosis, hypertension, buffalo hump, obesity, thin skin, amenorrhea, muscle weakness, mood changes, poor wound healing (remember: this looks like someone on chronic corticosteroid treatment-e.g., for chronic major arthritis or other inflammatory diseases)
393
What are the differences between Primary and Secondary Hyperaldosteronism?
Primary is called Conn syndrome, and has to do with an adenoma. You get Na+ retention and K+ excretion, Suppression of renin-angiotensin system, Women most often. Secondary typically results from renal disease, or cirrhosis. Increased renin stimulates aldosterone.
394
What is the percentage prevalence of adrenal cortical tumors?
They are very common, 1% of population has them. Most are nonfunctional.
395
What is more common, an adrenocortical carcinoma or adrenal adenoma?
Adrenal adenoma, the other ones are very uncommon.
396
What is a pheochromocytoma?
• It is a tumor of adrenal medulla (usually benign) –increases secretion of catecholamines • Can be episodic or sustain secretion • Effects typically look like increased sympathetic nervous system function • Hypertension • Flushing • Increased urine catecholamines
397
What is an adrenal neuroblastoma?
• Usually children Metastatic Can secrete catecholamines
398
What is another name for Paget Disease of Bone?
Osteitis Deformans. It is the second most common bone disease after osteoporosis.
399
What is the cause of Paget Disease of Bone?
Cause not known, but may be triggered by viral infections
400
What are the main features of Paget Disease of Bone?
• Common (3-4% Caucasians)- second most frequent bone disease after osteoporosis; chronic • Usually \>40 years of age; usually male • Often asymptomatic, can cause bone pain and fractures • Can cause arthritis if near joint • High serum alkaline phosphates • Vertebrae, skull and long bones common sites • Enhances osteoclastic activity—some rebound osteoblastic response; Described as a disorder of bone remodeling. • Often seen patches of radiolucency on radiographs
401
What is the definition of Diabetes Mellitus?
A relative or absolute deficiency of insulin, causing glucose intolerance.
402
What percent of world population has Diabetes Mellitus? US? How many die annually in US because of it?
3%, 8-9%, 73,000
403
What percent of population is in the prediabetes state? And what are the cutoffs?
14%, 41 million in US. • 75 gm glucose tolerance test: glucose \>200 mg/dL after 2 hours • HbA1c\>6.5% (this determines the extent to which your hemoglobin is glucosylated-it provides a good estimate of the average level of glucose for the previous 3 months:
404
What does the HbA1c measure?
When the body processes sugar, glucose in the bloodstream naturally attaches to haemoglobin. The amount of glucose that combines with this protein is directly proportional to the total amount of sugar that is in your system at that time. Because red blood cells in the human body survive for 8-12 weeks before renewal, measuring glycated haemoglobin (or HbA1c) can be used to reflect average blood glucose levels over that duration, providing a useful longer-term gauge of blood glucose control. If your blood sugar levels have been high in recent weeks, your HbA1c will also be greater.
405
What are some of the negative consequences that diabetes does to the body?
• Causes abnormal glucose management and metabolism • Protein catabolism • Abnormal adipocytes • Triglycerides in muscle and hepatic tissue • Increased inflammatory cytokines • Increased thrombosis and arthritis
406
What are the typical symptoms of type I diabetes?
• Polydipsia & polyphagia (hunger and thirst) • Polyuria (lots of diluted urine) • Unexplained weight loss
407
What are the physiologic functions of Insulin?
• Promote transport of glucose and amino acids through membranes of skeletal/smooth/cardiac muscle cells, fibroblasts, FAT cells (this is most important because can cause diabetes by selectively blocking insulin effects in fat cells ; it is an anabolic hormone • Does not affect glucose uptake in: neurons, kidney and red blood cells, retina, lens • Insulin and C-peptide (are linked in precursor peptide) are secreted from beta cells in islets of Langerhans (pancreas) in response to glucose
408
How are fat cells normally formed and what happens in diabetes?
Glucose is converted to triglycerides in fat cells normally, but in diabetes lipolysis results in ketosis and triglycerides in blood.
409
What happens with glycogen, normally, and with diabetes?
Glucose is usually converted to glycogen, but with diabetes, glycogenolysis and gluconeogenesis take place instead.
410
What happens with proteins, normally, and with diabetes?
Usually insulin helps make proteins (anabolic effect), but with diabetes, protein catabolism of muscle happens.
411
What are the features of Type I diabetes?
1. Type 1 (insulin-requiring) a. features: young (3-20 yrs old), loss of islet beta cells, 5% of cases, typically thin • no natural insulin • loss of beta cells an autoimmune process-probably triggered by environment such as a viral infection • ketoacidosis (Use of fatty acids in metabolism results in formation of ketone bodies (acetone)) (ketone bodies such as acetone)-dehydration; deep labored breathing (caused by acidosis); nausea, coma
412
What are the features of Type II diabetes?
2. Type II DM, “adult onset”, Non-insulin dependent DM a. Features • 95% diabetics are type II • Insulin levels often normal, problem is resistance of insulin receptors to insulin stimulation • Correlates with excessive visceral fat (80-90% are obese): restricted diet controls ~20% of diabetic expression • Correlates with hypertension and risk for atherosclerosis • Metabolic syndrome (see below for details) • Some genetics-likely polygenic autosomal • Most over 30 yrs old, but increasing numbers of younger Type I DM patients due to obesity • Minimal ketones or acidosis, but very high glucose --Hyperosmolar coma—enough insulin to prevent lipolysis, but still have elevated glucose
413
What causes type III diabetes?
Pancreatitis
414
What causes type IV diabetes?
Gestational
415
What is the metabolic syndrome related to type II diabetes?
• Type II diabetes-insulin receptors refractory to insulin • Abnormal lipid metabolism-high triglycerides & LDL, low HDL • Hypertension • Increased risk for atherosclerosis • Prothrombic tendency (high fibrinogen) • Dyslipidemia (high triglycerides & LDL, low HDL) • Pro-inflammatory state
416
What are the main oral problems associated with diabetes?
1. Increased gingivitis and periodontitis and abscesses 2. Poor wound healing (issue with oral surgery or implants) 3. Abnormal infections such as thrush/candida 4. Xerostomia (increased caries) 5. Hypoglycemic event if patients don’t eat before experiencing the stress of a dental procedure
417
What are the features of gestational diabetes?
• Gestational diabetes-due to stress of pregnancy (3-10% of pregnancies) • Usually goes away after pregnancy, although type II diabetes can develop later • Can have problems with placenta and babies are abnormally large with excessive insulin secretion and early hypoglycemia causing fetal malformations (e.g., cardiac, CNS, renal and limbs)
418
What is the infant of a diabetic (gestational) mother like?
Baby tends to be large (macrosomia) – Insulin is an anabolic hormone Baby develops hyperplasia of islets – Early hypoglycemia must be anticipated Increased risk for fetal malformation, mainly if the diabetes is poorly controlled – Cardiac, CNS, renal and limbs
419
What are the seven main long-term complications of Diabetes Mellitus?
1. Ketoacidosis/hyperosmolar coma/urinary tract infections 2. Ophthalmic-swelling, cataracts, retinopathy, neuropathy, glaucoma and blindness 3. Accelerated atherosclerosis, unhealthy cholesterols and negative consequences on heart (e.g., MI), kidneys (e.g., glomerulosclerosis, pyelonephritis, etc.), brain (stokes) 4. Peripheral neuropathies –loss of touch and pain in extremities; gangrene and amputations of feet 5. Autonomic nerve dysfunction: abnormal GI motility; hypotonic bladder, increased UTI 6. More prone to infections, slow healing 7. Elevated HbA1c (reflects average blood glucose over prior 1-3 months
420
What are the four main organ complications of diabetes mellitus?
1. Heart-coronary artherosclerosis and myocardial infarctions (most common cause of death in diabetics) 2. Kidney failure—renal nephropathy 3. Brain- stroke 4. Eye-retinopathy, cataracts, glaucoma
421
What is the reversal agent for the intrinsic pathway (PTT and Heparin)?
Protamine (+), which binds to (-) heparin and inactivates it.
422
What is the reversal agent for the extrinsic pathway (PT and Warfarin)?
Vitamin K. And Coumadin/Warfarin are very inexpensive.
423
What is coagulation factor II?
Prothrombin
424
What is coagulation factor IIa?
Thrombin
425
What is coagulation factor I?
Fibrinogen
426
What is coagulation factor Ia?
Fibrin
427
Which coagulation factor does Heparin work on?
Xa, which converts Prothrombin to Thrombin (II to IIa)
428
Where does Warfarin work?
Works everywhere you have vitamin K - 2, 7, 9, and 10
429
What is normal PT time?
11-13.5 seconds
430
What is a normal INR?
0.8-1.1
431
What do patients on warfarin typically have for INR?
2.0-3.0
432
What is a normal PTT time?
25-35 seconds, patients on heparin may have PTT time 2-3 times higher than normal.
433
Enoxaparin
Low molecular weight heparin. Improved morbidity and mortality for cancer patients for DVT as compared to warfarin.
434
Warfarin
Oral Vitamin K antagonist, requires bridging when initiated, monitoring with INR, very cheap.
435
Heparin
Administered via continuous drip.
436
What is DIC?
Disseminated Intravascular Coagulation: if coagulation and fibrinolytic systems become dually activated. More common in instances of major tissue damage, cancer, OBGYN emergencies.
437
Clopidogrel
Is an anti-platelet aggregation agent, inhibits ADP pathway irreversibly.
438
Asprin
Blocks thromboxane A2 = blocks degranulation of platelets. Irreversibly acetylates COX.
439
Thrombolytics
• Dissolve clot • Drugs include: streptokinase and urokinase • Are potentially very dangerous and can cause hemorrhagic strokes • Don’t use unless formed clot is in a very dangerous place
440
What is the physiology of alcohol in the body?
• Affects GABA A receptors (although not an agonist)—ethanol interacts with other sedative/hypnotic drugs in a synergistic manner and can lead to OD deaths due to respiratory depression. • Increases release of dopamine and endorphin • Affects almost all organs: e.g., • Liver toxin-increases fat deposits and can cause fatty livers in the extreme -causes cirrhosis in ~5-10% alcoholics -bad combination with acetaminophen • Kidneys- it is a diuretic • G.I.- irritating to mouth through the intestines—causes inflammation and enhances chances of cancer -stimulates gastric secretions -food slows its absorption • Suppresses immune system/perhaps partially due to malnutrition • CVS- low doses increase HDL—high doses increase hypertension, coronary artery disease, and arrhythmias • Brain: order of effects--- cortex (cognition)-limbic (emotions and reward)-cerebellum (motor and balance)-hypothalamus (endocrine)-medulla (respiration and CV regulation) • Disrupts lipid membranes
441
What does 0.05% BAC mean?
Relax, reduced reflexes
442
What does 0.08% BAC mean?
Legally impaired to drive
443
What does 0.2% BAC mean?
Motor impairment and poor judgment
444
What does 0.4% BAC mean?
Coma
445
What does \>0.4% BAC mean?
Death
446
Which cells is the pancreas made up of?
Alpha cells (20% of mass) - Secretes glucagon Beta cells (75% of mass) - Secretes insulin Delta cells G cells F cells
447
What does insulin help prevent with type I diabetes?
It prevents diabetic ketoacidosis (excess release of fatty acids leads to toxic levels of ketoacids).
448
What are the five steps getting to insulin secretion?
1. Increased glucose binds to GLUT2 receptor on beta cell in pancreas 2. This leads to metabolism of glucose and increased ATP 3. This ends up closing the potassium channel by depolarizing the cell 4. Which then allows increase in Ca to the cell 5. Which allows insulin stored in vesicles to be released and leave the beta cells
449
What is pro-insulin?
It is a small peptide that when hydrolyzed, released C-peptide and insulin. That is where it comes from.
450
What is the half life of insulin?
3-5 minutes
451
While insulin receptors are found on most tissues, what are its three primary targets?
1. Liver 2. Muscle 3. Adipose tissues
452
What is insulin's effect on the liver?
1. Inhibits glycogenolysis 2. Inhibits conversion of fatty and amino acids to keto acids 3. Inhibits conversion of amino acids to glucose 4. Anabolic action (promotes glucose storage as glycogen)
453
What is insulin's effect on muscle?
1. Increased protein synthesis 2. Increased glycogen synthesis 3. Increased glucose transport
454
What is insulin's effect on adipose tissue?
1. Increased triglyceride storage
455
Why can't insulin be taken as a pill?
Metabolism
456
What are the three characteristics of insulin?
1. Onset - the length of time before insulin reaches the bloodstream and begins lowering blood glucose 2. Peaktime - the time during which insulin is at maximum strength in terms of lowering blood glucose 3. Duration - how long insulin continues to lower blood glucose
457
For which types of diabetes is insulin replacement required?
For all type I, and for severe cases of type II.
458
What is the most common strength that insulin is available in?
U-100
459
How is most insulin prepared for use?
Most formulations prepared in laboratory (i.e. genetics; from genetically modified benign e. coli-e.g., Humulin), but can still obtain animal insulin (e.g, bovine, porcine) for special cases
460
What are the five main types of Insulin used for diabetes?
(1) Rapid-acting (e.g., Insulin lispro): • Rapid onset, early peak action, duration ~4 hours • Taken immediately before meal (2) Short-acting (crystalline zinc- helps to delay onset and lengthen duration) (Novolin): • 30 min. onset, peaks 2-3 hours, persists 5-8 hours • Often combined with NPH (3) NPH (neutral protein hagedorn) • Immediate-acting • Absorption and onset delayed because insulin linked to peptide called protamine for delayed release after injection • Pharmacokinetic features: onset=2-15 hrs; duration=4-12 hours • Often mixed with other shorter acting insulins for both immediate insulin and sustained insulin needs. • Becoming less popular (4) Insulin glargine • Long-acting sustained insulin: no peaks and valleys • Good as a background insulin (5) Insulin determir • Long-acting • Background insulin
461
Insulin lispro
Is a rapid-acting insulin, mimics after meal insulin, rapid onset, early peak action, can be taken right before a meal, duration is about 4 hours so it prevents post-meal hypoglycemia.
462
Novolin (crystalline zinc)
Is a short-acting insulin, effects take 30 minutes, peaks at 2-3 hours, and persists 5-8 hours, helps to lengthen duration and delay onset
463
NPH (neutral protein hadedorn)
This is becoming less popular, but this helps more by trying to mimic the basal level o finsulin, it is considered intermediate-acting insulin. This is often combined with protamine to delay onset. Has onset of 2-5 hours and duration of 4-12 hours. Usually mixed with regular, lispro, aspart, or glulisine insulin and given two to four times daily.
464
Insulin Glargine
Long-acting "peakless" insulin, good background insulin, the attach arginine and glycine to make a complex that is soluble in acid.
465
Insulin Determir
Long-acting, good background insulin. Threonine has been dropped and myristic acid added to this to prolong the availability of insulin by increasing self-aggregation and altering albumin binding.
466
What are the three main delivery systems of insulin?
1. S.C. (subcutaneous) Injection 2. Portable pen injectors 3. Continuous S.C. insulin infusion (needs constant monitoring)
467
What happens when you take too much insulin?
You can get hypoglycemic, which involves tachycardia, bizarre behavior, seizures, convulsions, and coma. You can also get local irritation and subdermal atrophy.
468
What are the characteristics of type II diabetes?
It is non-insulin dependent diabetes, characterized by tissue resistance to the action of insulin combined with a relative deficiency in insulin secretion. Usually no ketoacidosis, except stressors (infections). May benefit from treatment with both insulin and other drugs.
469
What are the three mechanisms of oral anti-diabetic agents?
1. Bind to sulfonylurea receptors and stimulate insulin secretion (sulfonylureas) 2. Lower glucose levels by action on liver, muscles, and adipose tissue (biguanides, thiazolidinediones) 3. Other mechanisms: e.g., slow intestinal absorption of glucose (alpha-glucosidase inhibitors)
470
Tolbutamide
Is a 1st generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain because they can bind to carrier proteins in the blood, be dislodged by other drugs, leading to rapid increase in their activity and hypoglycemia.
471
Tolazamide
Is a 1st generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain because they can bind to carrier proteins in the blood, be dislodged by other drugs, leading to rapid increase in their activity and hypoglycemia.
472
Chlorpropramide
Is a 1st generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain because they can bind to carrier proteins in the blood, be dislodged by other drugs, leading to rapid increase in their activity and hypoglycemia.
473
Glipizide
Is a 2nd generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain but a lot less likely to cause hypoglycemia than 1st generation sulfonylureas.
474
Glyburide
Is a 2nd generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain but a lot less likely to cause hypoglycemia than 1st generation sulfonylureas.
475
Glimepiride
Is a 2nd generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain but a lot less likely to cause hypoglycemia than 1st generation sulfonylureas.
476
Repaglinide
Is a glitinide, that acts in a very similar manner to sulonylureas, but doesn't bind as strong. So it is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain.
477
Biguanide
Used to treat type II diabetes, also called Metformin. Mechanism not fully understood—decreases glucose production in the liver and likely increases efficiency of insulin binding • Advantage: insulin-sparing, does not provoke hypoglycemia when used alone • May prevent some of the CVS effects of type II DM • Side effect: GI irritation, B12 deficiency, not for use in alcoholics
478
Acarbose
Used to treat type II diabetes, is an alpha-glucosidase inhibitor. Slows the digestion and absorption of starch, disaccharides, etc. by inhibiting alpha-glucosidase in the brush border of the small intestines and pancreatic alpha-amylase. Side effects are bloating and flatulence.
479
Rosiglitaone
Used to treat type II diabetes, is a Thiazolidinedione. reduces insulin resistance (especially muscle and fat cells) in type II DM by targeting PPAR-y receptor. Also increased GLUT-4 expression. Side effect: bone loss in women, weight gain.
480
Pioglitazone
Used to treat type II diabetes, is a Thiazolidinedione. reduces insulin resistance (especially muscle and fat cells) in type II DM by targeting PPAR-y receptor. Also increased GLUT-4 expression. Side effect: bone loss in women, weight gain.
481
Glucagon
Is produced in alpha cells of pancreas. It increases gluconeogenesis. Used to treat severe hypoglycemia, a side effect of diabetes drugs usually in an emergency setting.
482
What is commonly used to help suppress appetite for weight loss?
Amphetamines
483
Phentermine
Is used for weight loss, is an amphetamine. Phentermine inhibits norepinephrine and dopamine uptake • Side effect: weight loss, dry mouth, hypertension, palpitation • Interactions with sympathomimetics like MAOIs and SSRIs (including vasoconstrictors in local anesthetics)
484
What is Qysmia?
It is a drug used for weight loss and it is a combination of Phentermine and Topiramate (anti-convulsant). Qysmia is contraindicated during pregnancy. Topiramate can give feeling of "fullness" through decreased GI motility, increased taste aversion, increased energy expenditure.
485
Lorcaserin
Is used for weight loss, 5-HT2C agonist, suppresses appetite in hypothalamus.
486
Orlistat
Is used for weight loss, is a lipase inhibitor. It diminishes fat absorption by the intestines.
487
Methimazole
Is a thioamide that is used to treat hyperthyroidism. It inhibits thyroid peroxidase reactions, blocks iodine organification.
488
Propylthiouracil
Is a thioamide that is used to treat hyperthyroidism and Graves Disease. It inhibits thyroid peroxidase reactions, blocks iodine organification.
489
Besides thioamides like Methimazole, what else can be used to treat Hyperthyroidism or Graves Disease?
Beta Blockers like Propranolol can inhibit T4 to T3 conversion, and help treat hyperthyroidism, and Radioactive iodine can destroy some of the gland to help out. A simple iodide can be given as well to inhibit organification and hormone release.
490
Levothyroxine
Simulates T4 and is used to treat hypothyroidism. The T4 products are prescribed more frequently and have fewer side effects because less potent.
491
Liothyronine
Simulates T3 and is used to treat hypothyroidism.
492
What are the three adrenocorticosteroids and what do they do?
1. Glucocorticoids - Regulate intermediary metabolism and immunity. Cortisol synthesized from cholesterol (hydrocortisone). 2. Mineralocorticoids - Aldosterone (Na retention/K+ loss). 3. Androgens - Dehydroepiandrosterone, DHEA, can be converted to estrogens.
493
What is the mechanism of hydrocortisone?
It regulates transcription of target genes in nucleus to alter synthesis of inflammatory proteins. In plasma, In plasma, corticosteroid- binding globulin (CBG) binds 90% of the circulating hormone under normal circumstances. When plasma cortisol levels exceed 20–30 mcg/dL, CBG is saturated, and the concentration of free cortisol rise rapidly. Half-life is 60 minutes.
494
What are some common uses of cortisol?
• Severe allergic reactions • Relieve inflammatory bowel disease • Relieve severe arthritis • Relieve bronchial asthma • Relieve severe dermatitis
495
What are the main effects of glucocorticoids (cortisol) on the body?
Stimulates gluconeogenesis and glycogen synthesis in the fasting state. Increases serum glucose levels and thus stimulates insulin release. Supraphysiologic amounts of glucocorticoids lead to decreased muscle mass and weakness and thinning of the skin. Increased insulin secretion stimulates lipogenesis and to a lesser degree, inhibits lipolysis, leading to a net increase in fat deposition. Suppresses synthesis of inflammatory cyotkines. Can cause osteoporosis in Cushing's syndrome.
496
What are the side effects of systemic glucocorticoids?
• Secondary infections • Mood and behavioral disruption • Osteoporosis • Cataracts • Hypertension • Moon face • Buffalo hump
497
What are the short-to-medium acting glucocorticoids?
Hydrocortisone, cortisone, prednisone
498
What is the long-acting glucocorticoid?
Dexamethasone
499
What is and what are the symptoms of Addison's Disease?
Addison’s—adrenal glands produce too little cortisol (chronic)—often insufficient aldosterone as well • Symptoms • Weakness • Fatigue • Weight loss • Hyperpigmentation • Treatment—corticol supplements: cortisones (hydro-) or prednisone
500
What is Cushing's syndrome?
Chronic high levels of the hormone cortisol, usually due to ACTH-secreting tumor. Symptoms include • Buffalo hump (fatty deposits on upper back between shoulders • Osteoporosis • Hypertension • Emotional
501
Ketoconazole
Used for Cushing's syndrome. Inhibits adrenal steroid synthesis.
502
Metyrapone
Used for Cushing's syndrome. Reduces cortisol synthesis by inhibiting steroid 11-hydroxylation.
503
Mifepristone
Used for Cushing's syndrome. Is an antagonist at steroid receptors.
504
What are the main two mineral components of bone and two most important minerals for cellular function?
Calcium and Phosphate
505
What secretes Parathyroid Hormone?
Chief cells of the parathyroid glands
506
What secretes Calcitonin?
Parafollicular cells of the thyroid gland.
507
What is 1,25-Dihydroxycholecalciferol?
It is a steroid hormone formed from vitamin D which undergoes hydroxylations in the skin catalyzed by then sun followed by successive hydroxylations in the liver and kidneys. Its primary acLon is to increase calcium absorption from the intestine to increase Ca2+ in serum and bone.
508
What does parathyroid hormone do?
Its main acLon is to mobilize calcium from bone to increase serum Ca2+ and and increase urinary phosphate excretion.
509
What does calcitonin do?
Inhibits bone resorption & stimulates renal secretion to reduce serum Ca2+ levels.
510
Does PTH and 1, 25-(OH)2D act on osteoblasts or osteoclasts?
Has direct effects on osteoblasts (rapid); also stimulates expression of the protein RANK ligand receptor (RANKL), which then activates the osteoclasts. Thus indirect effect on osteoclasts is slower.
511
Denosumab
Is a monoclonal anti-RANKL antibody treatment of excess bone resorption in osteoporosis and some cancers. it prevents RANKL from stimulating osteoclast differentiation and activity.
512
Teriparatide
Treats osteoporosis by selectively activating osteoblasts. It is the first and only drug that stimulates new bone formation. Contraindicated in individuals at risk for osteosarcoma, Paget's disease, because it is associated with risk of osteosarcoma.
513
Vitamin D
Regulates gene transcription via the vitamin D receptor; Regulates intestinal calcium absorption, bone resorption, renal calcium and phosphate reabsorption; decreases parathyroid hormone (PTH) production. Net effect is increased serum calcium and phosphate levels. It is used clinically for osteoporosis, osteomalacia, renal failure. Adverse effects include hypercalcemia, hypercalciuria.
514
What are the two categories of Osteoporosis Medications?
1. Anti-resorptive medications (slow bone loss) 2. Anabolic drugs (increase rate of bone formation)
515
What are the three medications used for anti-resorptive medications for osteoporosis?
1. Bisphosphonates 2. Calcitonin 3. Denosumab
516
Ibandronate
Is a bisphosphonate taken monthly that inhibits osteoclasts, thereby slowing bone loss. Used in the prevention and treatment of osteoporosis, Paget's disease, bone metastasis (with or without hypercalcemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, and other conditions that feature bone fragility. Be careful of osteonecrosis of the jaw though after IV administration of bisphosphonates.
517
Alendronate Sodium
Is a bisphosphonate taken daily that inhibits osteoclasts, thereby slowing bone loss. Used in the prevention and treatment of osteoporosis, Paget's disease, bone metastasis (with or without hypercalcemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, and other conditions that feature bone fragility. Be careful of osteonecrosis of the jaw though after IV administration of bisphosphonates.
518
Teriparatide
An anabolic drug that increases the rate of bone formation, used for osteoporosis, is a synthetic form of parathyroid hormone. It activates osteoblasts.
519
What are the four secondary hormonal regulators of bone mineral homeostasis?
1. Calcitonin - lowers serum calcium and phosphate 2. Glucocorticoids - Antagonizes Vitamin D stimulated intestinal Ca transport, net effect of lowering plasma calcium. Common cause of osteoporosis in adults when used too long. 3. Estrogens - Prevents bone loss in early postmenopausal period. 4. Selective Estrogen Receptor Modulators (SERMs) (e.g., Raloxifene) - Used for osteoporosis as well. -Fibroblast growth factor is also a regulator.
520
Cinacalcet
Activates the calcium sensing receptor in the parathyroid gland to inhibit more PTH secretion to decrease serum Calcium.
521
Hydrochlorothiazide
Is a thiazide diuretic that reduces renal excretion by increasing calcium reabsorption at the distal tubule.
522
What is osteopetrosis?
Osteoclasts are defective and thus unable to resorb bone, bone density increases and growth becomes distorted.
523
What is osteoporosis?
Excess osteoclast function results in loss of bone matrix and risk of fractures. Involutional osteoporosis is when you get older and your bone loss increases. Treatments include bisphosphonates which inhibit osteoclasts and increase mineral content of bone.
524
What is Rickets (children) and Osteomalacia (adults)?
Defective bone matrix calcification due to Vitamin D and or Calcium deficiency. Treatment involves replenishing vitamin D and calcium.
525
What is Paget Disease of the Bone (Osteitis Deformans)?
• Osteoclast are more active than osteoblasts leading to malformed bones-large, dense and brittle. Osteoblasts become overreactive and make excess bone that is very chaotic, weak, brittle, and deformed. Treatment is Alendronate Sodium.
526
Difference between primary and secondary adrenocortical insufficiency?
Primary - weakness, nausea, hyperpigmentation of skin, hyponatremia, hyperkalemia, adrenal crisis is when steroids are needed right away, waterson-friederichson syndrome is a hemorrhage into cortex from menigococcal infection. Addison's disease.
Secondary - no hyperpigmentation, aldosterone is normal, due to steroid treatment.
527
Difference between primary and secondary hyperaldosteronemia?
Primary - adenoma caused, sodium retention and potassium excretion. Secondary - results form renal disease or cirrhosis.
528
What is high serum alkaline phosphates associated with?
Paget's disease
529
Glucocorticoids antagonize the effects of Vitamin D. True or False?
True
