Drugs That Effect the Cardiovascular System Part 1 (Simplified as much as is humanly possible)

This post is another that's mostly for personal reference (and amusement). I've tried to put silly pictures so it's "fun" AND "educational". Notes are compiled from Roache's Introductory Clinical Pharmocolgy, supplemented with my own nursing knowledge (and wikipedia). 

If you notice any errors, please bring them to my attention.

Anti-Hypertensive Drugs-
(These are drugs that make your blood pressure decrease)

Video On Antihypertensive Therapy-More Detailed Explanation

• Diuretics:

• Hydrocholothiazide (Lasix), Bumetanide (Bumex), Mannitol (Osmitrol), Spironolactone, Acetazolamide (Diamox)

• Lower the volume of blood circulating in the blood vessels (by making you pee out water and electrolytes).

• Beta-Adrenergic Blockers:

• Atenolol (Tenormin), Metoprolol (Lopressor), Acebutolol (Sectral) and Propranolol (Inderal) 

• Block epinephrine receptor sites (decreasing stimulation of sympathetic "fight-or-flight" nervous system). It makes your heart slow down and your arteries dilate (which is weird, because beta receptor activation makes your arteries dilate anyways) it's kind of like telling the cells in your heart, kidney etc. to chill-out. 

• Calcium Channel Blocker
• 
  Verapamil (Calan), Nifedipine (Aladat, Procardia),  Nifedipine (Aladat, Procardia), Amlodipine (Norvasc), Diltazem (Cardizem)

• Blocks calcium from causing contraction/constriction of smooth muscle (so our arteries don't constrict)
• ACE Inhibitors:
• Benazepril (Lotensin), Captopril (Capoten), Enalapril (Vasotec), Lisinopril (Zestril), Quinapril (Accupril), Ramipril (Altace).

• Prevent/inhibit the activity of an enzyme that is involved in the synthesis of a potent hormonal constrictor.

• Angiotensen II Receptor Antagonists
  •  (ARBs) Losartan (Cozzar), Valsartan (Diovan)

• Block the potent hormonal vasoconstrictor from it's receptor site

• Human B type Natiuretic Peptides (B-N-P...just like the lab!) :
• Hormone (made in the heart) that dilates veins and arteries (We can make it synthetically as a drug too?)

I don't have a picture of this one so here is a cat:

• Alpha Adrenergic Antagonist 

• Clonidine (Catapres), Methyldopa, Guanfacine
• Blocks receptor norepinephrine (blocking the "fight-or-flight" response that causes vasoconstriction)

(For more info on the difference between alpha and beta receptors: Click Here)

• Direct Acting Periperal Vasodilators
• Hydralazine (Apresoline), Nitroprusside (Nitropress), Minoxdil (Loniten)
• Activates Potassium Channels in the peripheral vessels, preventing calcium from making the vessel contract.

Anti-Arrhythmic Drugs-

There are several different subtypes of drug this classification, and each of them has a different mechanism of action, but but all of them suppress irregular heart rhythms. In general they slow conduction and keep the electrochemical status of the cellular membrane so that it is only stimulated by the dominant pacemaker (and not irritable foci)

(Watch these videos to learn about voltage gated channels)

Class I: The Sodium Channel Blockers (I like to think of them as Membrane Stabilizers)

• Class IA Drugs
• Drug examples: Disopyramide (Norpace), Procainamide (Procanbid), Quinidine (Quinaglute)

• Class IB Drugs
• Lidocaine (Xylocain)

• Class IC Drugs
• Flecainide (Tambocor) and Propafenone (Rythmol)

Class II: Beta Adrenergic Blockers

• Acebutolol (Sectral) and Propranolol (Inderal)

• (Beta Blockers are anti-hypertensive and anti-arrhythmia :P). As I discussed above, these drugs block receptors for catacholamines like epinephrine and norepinephrine, decreasing sympathetic stimulation. They also promote the release of another hormone in the kidneys: renin (which lowers heart rate and blood pressure, also has a membrane stabilizing effect), blocks calcium channels, and also blocks catecholamine caused dysrhythmias. 

• Class III: Potassium Channel Blockers

                                                       

• Amiodarone (Cordarone), ibutilide (Covert). 
• Interfere with potassium conduction at a specific phase in the action potential cycle (see video)

• Class IV: Calcium Channel Blockers

• Diltazem (Cardizem), Amlodipine (Norvasc), Nifedipine (Aladat, Procardia), Verapamil (Calan)
• Interfere with calcium conduction at a specific phase in the action potential (see video)

Cardiotonic Drugs-

Just like healthy skeletal muscles, healthy heart muscle has a certain degree of firmness-even when it is relaxing. 

Toned muscles are stronger, they contract more effectively, and they are less likely to experience fatigue when put under the stress of physical activity.

Toned Cardiotonic drugs help flabby heart muscle get toned.

Improving cardiac output, and making it more effective as an organ.

The Cardiotonic Drug Digoxin does this by slowing the heart down.

(Negative Chronotropic Activity)

and slowing the heart's electrical conduction through AV node

(Positive Intropic Activity)

(You'd think it would be the other way around, that more electrical activity would mean a more toned heart, but that's not the case, especially when the electrical activity is not as organized. (A. Fib) An organized rhythm with enough force of contraction to deliver optimal cardiac output is more important then a fast heart rate. Coincidentally, endurance athletes have a lower heart rate for the very same reason: their hearts are toned enough to deliver an adequate cardiac output with fewer heartbeats).

If you are giving a Cardiotonic it's important to remember to check the patient's heart rate before administering and to not give the drug if the patient's heart rate is already bradycardic.

Just for fun, did you know where digoxin comes from?

It's a (poisonous) flower!!!

You know what it does? It makes your heart beat slower (gasp!)

And it is POTENT! The concentration of most other drugs is measured in milligrams, the concentration of digoxin is measured in micrograms.

If the patient has only just started taking the drug, or if s/he has kidney problems, it's important to monitor for digoxin toxicity:

On the EKG:

In Labs:

(Elevated serum digoxin levels)

And other symptoms like bradicardia, drowsy, nausea, vomiting...

If the patient has a massive digoxin toxicity s/he will need the digoxin antidote-

Digoxin immune fab (AKA Digibind).

Here's a website I thought was cool: http://abcmaps.tumblr.com/page/2

T: Trauma

Here is a link to a PDF that talks about resucitstion of a trama victim: http://www.google.com/url?sa=t&source=web&cd=9&ved=0CEoQFjAI&url=http%3A%2F%2Fwww2.warwick.ac.uk%2Ffac%2Fmed%2Fresearch%2Fhsri%2Femergencycare%2Fprehospitalcare%2Fjrcalcstakeholderwebsite%2Fguidelines%2Ftraumatic_cardiac_arrest_2006.pdf&ei=HplfU6elJoOayAS1u4LwBA&usg=AFQjCNF5Le8OaJfeAsWN4v2ktDkcYivKWQ

Different things have to be taken into account in a trauma victim then a CHF patient. You still analyze theit heart rhythm and defibrillate/start compressions but if they are actively bleeding you don't do it as long, esspecially not if they aren't showing signs of improvement.

I've heard several horror stories but, thankfully,  I've never had to do CPR on someone with penetrating trauma.

T: Tamponade, Pulmonary

I could only find one source on Pulmonary Tamponade. Most of the documents on H' and T's don't even mention this one.

:(

According to the UCSF Children's Hospital Intensive Care Nursery House Staff Manual, Pulmonary Tamponade is a complication of intubation. If ventilator settings are too high, the lungs become over expanded and air gets trapped in them. The Chest wont move as much, CO2 will be high, O2 will be low, and blood pressure will decrease.

Settings will need to be adjusted (which I have no idea how to do, so until I learn about respiratory therapy I'm going to leave it at that).

Disconnect vent for about 5 seconds while you reset to allow lungs to expell air.

T: Tamponade, Cardiac

Cardiac Tamponade is usually a complication of an inflammatory response in the sac that holds the heart and keeps things in your chest from rubbing together (pericarditis).

Inflammation in this area can cause fluid to leak from the vascular compartment to the extravascular space (from the blood vessels into the tissues). The fluid buildup within/beneath the pericardial sack constricts the heart chambers, keeping them from filling completely and subsequently reducing cardiac output.

Sometimes a viral, bacterial, or fungal infective agent is identified. Other times heart surgery or autoimmune disease  (coocommittant with other illnesses like AIDS or tuberculosis) can be identified as a cause. But many times the exact cause is not easily identifiable.

Diagnostic tool is a echocardiogram.

Treatment is pericardiocentisis.

T: Toxins

Toxins-

Sometimes when I think of toxins I only think of pollutiants and posions, like gasoline fumes or a snakebite, but substances that are normally thought to be helpful (like many therapeutic drugs) can also cause toxicity in high doses. It is importiant to get an accurate patient history; including therapeutic and non therapeutic drug use, circumstances surrounding the admitting complaint.

Each toxins mechanism of action is going to vary, but it's still importiant to be familiar with the most common types in case you have a patient who looks like they might code and evidence of the other"H's & T's" are not present. Some toxins disrupt metabolism, others cause cells to break apart, but many of the most common toxic reactions originated from a therapeutic drugs pharmacological reaction accentuated by other factors: Liver failure, kidney failure, accidential or intentional overdose (or a combination of the three).

I've found several PDF's and other graphs that are wonderful educational material to communicate toxin mechanism of action and antidote, once I get back on PC I will update thene here.

Luckily, many pollutants, posions, and drug toxins have antidotes and the effect can be reverse if its cought early enough:

Acetamenophen (Acetylcystine AKA "Mucomyst")
Digoxin (Digoxin immune FAB)
The Blood Thinners
-coumadin (vitamin K)
-heparin (Protamine Sulfate)
Narcotics: Dilaudid, Morphine etc (Narcan)  
Arsonic (Dimercaprol)
(In some instances, dialysis is appropriate)

Drug-toxins may have specific effects on vital organs that, when outside of therapeutic range, cause a characteristic disfunction. I spoke about two of them in "Matters Of The Heart: Drug and Elecrolyte Imballance"

H: Hypoglycemia

Without adequate glucose suppy cells will not be able to carry out metabolism and will die. However, hypoglycemia is not always considered part of the "H's and T's"

One reson for this is that most of the body's cells (the heart included) will usually find an alternate method of metabolism (for instance glycogen, fat or protiens etc.) so even when you're not eating, you still have access to energy.

Another is that the heart will not be the first organ to fail when glucose is very low. The brain will because it cannot metabolize any other source of energy besides glucose.

A hypoglycemic person eventually will suffer from cardiac arrest, but first they'll feel tired, maybe a bit cranky (maybe have a seizure) and pass out (sometimes it looks like they just went to sleep, this is why the nurse will wake you up to check your blood sugar)

...AND THEN they'll stop breathing.

The most common condition to precipitate profound hypoglycemia is insulin overdose in a diabetic patient. This is why many hospitals have introduced protocol for two licensed nurses to verify the insulin type and dose before administration (and also why nurses can be very anal about making sure you eat after you take your insulin, they're just trying to keep you safe!).

I had a habit of checking the drug, dose, time and patient before giving insulin from nursing school so it was a bit of an adjustment not having that protocol at my first job. I got in the habit or doing that with the patient whenever possible. Sometimes they are too confused or it pisses them off, but I think it's really importiant to get it right.

If a nurse gives a fast acting insulin and the patient doesn't eat right away, the blood sugar will drop. If the nurse gives a longer acting insulin & a regular insulin the patient might have hypoglycemia in the early morning before breakfast. (depending on the level of functioning the pancreas has, remember if your type 2 diabetic your pancreas is still making some of it's own insulin and that has to be factored in to your insulin dose...but I'll save that for a later post.)

This is why the nurse pokes your finger so much.

Yes, I'm sorry I hate to do it :-(

Luckily there is an antidote for hypoglycemia. Because insulin is a naturally occuring hormone, it is counteracted by another naturally occuring hormone called glycogen...which is availible in commercial drug form as glucagon gel (squirted on the gums) or give intramuscularly. (It works pretty quickly!)

So even though its not part of the "H's and T's" its still a good idea to check a patient's blood sugar if you're concerned they are deteriorating, esspecially if they are diabetic and recieving insulin therapy.

Hyper/HypoKalemia

Not long ago I worked in a SNF (Skilled Nursing Facility). It's the type of place people go when they are not sick enough to stay in the hospital and not well enough to live at home.
A part of my job there involved responding to laboratory reports recieved from the laboratory center via fax.

One day, after doing my first rounds and recieving report I checked the fax for these lab reports. I noticed a report for a particular patient in the stack of papers, it was for a BMP (Base Metabolic Panel, or Electrolyte Panel) and the results were listed as "Pending"

This is not a rare occurance. Sometimes if lab results aren't complete, it's nice to get a notice that they're still working on it, that they haven't been missed or forgotten.

Later on that evening I checked the fax machine again and there was another lab report for the same patient. The report still was marked "Pending".

It is a bit weird to have a rutiene lab take that long, esspecially when all the other labs that were collected at the exact same time as this one had already come back.

The patient was alert and verbally responsive throughout the evening, participating in self care and complaining of only chronic pain.

Early in the morning, the CNA providing care in the room saw the patient become unresponstive and stop breathing. A pulse could not be felt. We started CPR and called 911. The patient was taken to the hospital in cardiac arrest.

I spent a lot of the rest of the morning calling people and documenting what had happened. 

The whole event was unanticipated and upsetting, esspecially when I heard the fax machine printing out another set of papers.

They were lab results for the patient who had just been sent out...

And they were still "Pending".

I later learned that the lab had reiceved the blood, and it had been processed, but the level of pottassium in the sample was so high that they did not accept it as an accurate reading. They called later in the day to say they were sending out another  phlebotimist to collect another sample because the pottassium level was abnormally high.

Pottassium is a mineral like salt, when it desolves in water it becomes an ion refered to as K+ (or K) it is primarily an intracellular ion involved in many processes including glucose transportation accross the cellular membrane and muscle function.

Low levels of K (hypokalemia) can occur during diuretic therapy in "pottassium wasting diuretics".

Hypokalemia is also associated with certian endocrine disorders: in diabetic patients, high levels of glucose are also associated with low levels of pottassium. In Cushing's Syndrome (when the adrenal gland is releasing too much of the steroid hormones cortisol and ACTH) the cells are put into "energy storing mode". Which causes conversion of glucose to storable forms of energy such as glycogen or fat, this also lowers the pottassium level as the glucose must be transported inside a cell in order for it to take place.

High levels of pottassium (Hyperkalemia) occur when a patient with renal problems is recieving a special kind of diuretic called a "pottassium sparing diuretic" or alternatively is recieving a supplemental pottassium vitamin at too high a dose.

It is also associated with hypoglycemia in diabetes and in Addisons disease-when the adrenal gland is releasing too little of the steroid-hormone cortisol or ACTH, causing the cells to be in energy consumption mode-this condition leads to low glucose levels and (...you guessed it) hyperkalemia.
People with Addison's disease will need to take steroid replacement drugs long term, unfortunately long term steroid replacement is associated with

Cushing's Syndrome

:(

There is a very narrow therapeutic range for pottassium (3.5-5.0 mEq/L), so a patient with a blood pottassium level of 7 mEq/L has a critical value for that lab. People with critical values for pottassium are in extreme danger of suffering from life-threatening arrythmias.

Now, it is possible to get a false critical value. Sometimes if a blood sample sat out too long the blood cells lyse (break apart) and all the intracellular pottassium gets mixed up with the extracellular pottassium, making the overall reading to be higher. When this happens, another sample needs to be collected.

Hypokalemia causes the heart to repolarize very, very slowly. This means that the T wave (the beginning of repolarization) will be flat and there will be another wave between it and the P wave of the next PQRST complex. This new wave is called the 'U' wave. If the patient does not recieve supplemental K via pills or a diluted dose IV, Torsades de Pointes will develop (a particular type of V Tach)

Hyperkalemia causes the heart to take a long time depolarize, resulting in flat P waves, a wide QRS complex and peeked T waves.  Eventually this will also deteriorate into V Tach and V Fib, if its not dialized.

Pottassium is an importiant lab to monitor. If you have a high or low reading (even if you think its false) its importiant to communicate it. I'm not even being dramatic when I say its a matter of life and death. The worst that would have happened in an innacurate lab draw is the patient got sent to the hospital and monitored closely until the pottassium level was verified.

H: Hydrogen Ion Excess (Acidosis)

This one is always hard for me to remember. Partly because it DOESN'T ACTUALLY START WITH AN H!!!! and also because I view it as a side effect, not a cause.

Acids are a waste product of metabolism. Particularly anabolic/anaerobic metabolism (which is the kind that occurs in the absense of oxygen...so as you can imagine, a patient recovering from cardiac or respiratory arrest will have a lot of acid in their body!)

In an anaerobic state, the cells are trying to keep working, even though they don't have oxygen to act as the catalyst for the metabolic pathway that results in energy. So, they make it out of other molecules...with hydrogen's left over as junk.

In high concentrations, hydrogen acitic damage the cells. (A fact which I've pretty much taken for granate for many years, as the focus of most educational material I've exposed myself to is on acidosis (the process of producing acid) and not acidemia (the acidotic state itself))

There are two main ways the body rids itself of these acidic molecules:

Lungs via Breathing (fast acting)

Kidneys via Diuresis (slower response)

Your body produces acid when you exercise or when your body is under stress (think of leg cramps or 'burning' muscles after running) but most of the time a healthy person can deal with this by breathing more heavily...and even though you might feel sore for a couple of days, eventually your kidneys rid your body of the rest of it and it's not a problem.

Acid production is normal, it only really becomes a problem if your kidneys or lungs are diseased. This is why I often think of acidosis as a side effect, not a cause. However, it is an independent factor to consider when dealing with a  when dealing with a cardiac arrest scenario.

If the patient has been in respiratory distress, and/or is suffering from kidney failure. Acidotic condtions may persist even after optimal oxygenation has been re-established (or alternatively, kidney function has been re-established via diuretic/dialasis use) because the acid produced is still too much for the body to handle.

Most of the people I have seen who suffered from acidosis (or 'Hydrogen Ion Excess') were already very sick and experienced this condition secondary to the initial illness. It's importiant to monitor the acutely ill patient for this complication.

(Now that I think of it, I believe one individual who was suffering from alcohol overdose and malnutrition also had a form of acidosis. And people who are diabetic can suffer from ketoacidosis...hmm)

Labs that are vital to assess in a patient suffering from this type of problem are the Blood Gas Analysis. There are guidelines to help determine if the patient's acidotic/alkalotic condition is caused by respiratory failure or kidney failure depending on the ratio of the the kidney capacity indicator HCO3 and ventilation capcacity indicator PCO2, but I'll save that for the hypothetical respiratory therapy post because it's complicated and I don't feel like explaining it right now.

(Ketones, alcohol and lactic acid would probably be importiant too.)

The treatment for acidosis is dependant on the cause (if it is due to respiratory failure, the patient might need to be on a ventilator. If it is due to kidney failure, the patient might need dialysis.) The only emergency drug to treat acidosis is the base-Sodium Bicarbonate and it has been taken out of ACLS protocol and is only used under special cirumstances.

H: Hypoxia

Hypoxia just means the tissues of the body are not getting enough oxygen to function.

Hypoxia can also occur peripherally due to factors such as anemia, CHF, PAD, emboli or CO poisoning. (but we won't talk about those right now) I'm pretty sure the type of hypoxia they are talking about involves ventilation and gas exchange at the lungs.

There are MANY causes of hypoxia, here are a few I could think of:

Enviornmental: Decrease in inspired oxygen not secondary to organ failure. For instance, suffication (blocked airway) or high altitude.

Hypoventilation: A decrease in inspired oxygen due to altered ventilation pattern. Narcotic OD, or neurologic damage to respiratory drive.

Airway Inflammation/Increased Resistance  to Airflow: occurs in Asthma, Emphysema, Anaphlaxis, and Bronchitis.

Impared Gas Exchange at alevolar/capillary membrane-

Alveoli are blocked, collapsed or swollen: Pneumonia, Aspiration, Pneumothorax, Pulmonary Edema.

The alveolar membrane becomes thick:  emphesemia, Acute Respiratory Distress Syndrome, and Pulmonary Fibrosis. This inhibits gas exchange from the alveoli to the capillary.

Shunting (bypassing alveoli altogether): Anatomical heart defect, pulmonary edema, or atelectisis (alveoli collapse). 

Ventilation/Perfusion (V/Q) missmatch: Pneumonia.

Look for signs and symptoms of respiratory distress...

Not breathing

ANY difficulty breathing...rapid, slow, shallow, deep, involving rib cage

Restlessness and anxiety (eventually progressing to lethargy and coma)

Pale/blue skin-esspecially fingers or lips

Pulse Ox reading low. (Usually below 91 in adults is abnormal, however patients with known lung disease like COPD may have "normal" baseline that is below that)

Cold skin

Elevated BP

Elevated HR (eventually progressing to bradycardia)

Arterial Blood Gas Analysis

If the patient happens to be on a ventilator, there are a whole different set of things to monitor that belong on a respiratory therapy post.

H: Hypothermia

Hypothermia occurs when the body's core tissues become cold; usually 95 degrees F (35 degrees C) or colder.

(Core body tempuratures are usually measured in the rectum, esophagus, or bladder)

Low body tempuratures inhibit cellular metabolism, and cardiac arrest can result if optimal tempuratures are not restored.

Normally when I think of hypothermia, I think of exposure to extremely cold elements (like freezing water or snow) being the cause. But I live in the desert and the only times I've ever seen it is in people suffering from alcohol overdose. It is also a risk in people suffering from sepsis, when the thermo-regulation mechanism in the body has failed...or in the homeless population. In general, people who are ill, exposed, and cannot meet their own needs are at risk.

(Optimal body tempurature is usually 97.7-99.5 degrees F.)

There are four degrees of Hypothermia. Depending on the severity, the patient will need to undergo rewarming measures:

Mild: 90-95 degrees F. (Passive rewarming, remove cold or wet clothing and apply dry and warm covering. Allow patient's body provide it's own warmth)
Moderate: 90-82 degrees F. (Active external rewarming, forced air device over body or heat packs to underarms and groin...if you wanna be getto like that ;))
Severe: 82-68 degrees F. (Active internal rewarming, warm IV fluids I believe at a temp of 100.4 degrees F is recommended, but I'm not positive)
Profound: < 68 degrees F

I mentioned above that cardiac arrest can occur in hypothermia because cellular metabolism is inhibited. Because the cells have stopped working, any drugs you give the patient when the body tempurature is extremely low will not work. This is a concern because if a patient is extremely cold (below room temp) and is recieving CPR, the drugs given as part of ACLS protocol won't have any effect. (The defibrillation shock probably won't work either)

Partly because of this, a patient cannot be declared dead until the body has been warmed to at least room tempurature, and cellular metabolism has been given the chance to resume.

There is a treatment called therapeutic hypothermia in which the body tempurature is lowered to 91 degrees F.after a period of hypoxia or stress, your hospital will have specific protocol for when and how to use this treatment.

H: Hypovolemia

There are two types of
Hypovolemia:

1) Absolute-meaning loss of blood or a blood component from the body

2) Relative-meaning pooling or compartmentalizing of blood or a blood component into one area of the body.

In absolute hypovolemia, blood volume has actually been expelled. The two most common causes are hemorrhage and diuresis.

When I think of hemorrhage, I usually think of laceration wound or car accident-blunt trauma, even blood loss that has been documented and monitored from surgery can cause problems if it is not replaced.

But I've also seen many cases of gastrointestional bleeding that caused hypovolemia. Sometimes people have these ulcerations along their digestive tract and even if they've been there for a long time they can become super-irritated and bleed. If it's in the stomach, and the blood loss is acute, the patient might vomit frank blood or curdled blood. If it is a slower, 'chronic bleed' it might pass through the GI tract and come out the other end so it's importiant to examine stool. If its from the stomach or early in the digestive tract, it will be partially digested. Digested blood isn't red, it's dark and tarry.
If the stool has reddish streaks or you see blood then the bleed occured later in the digestive tract.

Whole blood may be lost via hemmorrage, but loss of blood components can also cause hypovolemia. This is the case with diuresis.

Interstial fluid (the fluid component with electrolytes) is lost during kidney diuresis so excessive diuretic use, or a pituitary disorder called diabetus inspitus which mimics this effect, can cause hypovolemia. It is also lost when excessive vomiting or diarrhea occurs. 
  
One other blood component that can be lost is plasma. In severe burn injuries, the protien-rich plasma is lost, contributing not only to volume loss but to REALTIVE loss of fluid from circulation.

Relative Hypovolemia-

There can be a suficient amount of fluid in the body (or even an excess of fluid) and the patient can still be dehydrated/hypovolemic. This is because blood is stuck in one area of circulation and is not circulating as it should.

Third spacing-If systemic blood pressure is insufficient (CHF, Hyper/hypotension), if electrolytes are unballanced (Hypo/hypernatremia), if plasma is lost (severe burns), if an organ is infected or suffering from inflammation (ascites, bowel obstruction, peritonitis et all)...fluid will accumulate outside of the blood vessels.

Internal bleeding-Internal injury (such as fracture, organ rupture,  can cause hemmorrhage that causes blood to accumulate outside of the blood vessels.

In addition, Massive Vasodillation (such as that triggered by sepsis) can trap blood inside the larger vessels, so blood can't perfuse the capillary bed. 

Some of the signs and symptoms of hypovolemia will depend on the cause (Eg. Diarrhea, low urine output, etc) but some hallmarks are to keep in mind are:

Complaints of thirst-
Elevated heart rate-
Elevated respiratory rate-
Decreased urine output-
Decreased skin turgor/flat neck veins/dry tongue

LABS-Dehydration will show a high degre of solutes (hemglobin/hematocrit, electrolytes, etc.) and a low degree of solution. Also look for sirum protiens outside of normal limits.