Concepts in Medicine

The Low Energy State:

This is the most fundamental principle to understanding so much medicine. Over 90% of all illnesses fall into this category. When the body undergoes starvation, malabsorption, storage diseases, vitamin deficiencies, etc. due to a pathologic state; the body responds by conserving the energy it has to help the body heal, leading to a low energy state. Since every cell in your body has need of energy (ATP), any disease that interrupts its ability to supply energy (ATP) will affect every cell in your body, especially CNS, muscles, primary active transport, cardiac function and rapidly dividing cells (skin, hair, cuticles, GI, renal PCT, respiratory epithelium, bone marrow, endometrium, germ cells, bladder and vascular endothelium). This causes the following symptoms: CNS: mental retardation, dementia CV: heart failure, pericardial effusion Muscle: weakness, shortness of breath, vasodilation, impotence, urinary retention, constipation, etc. Primary Active Transport (ATPases): Stop Working Rapidly Dividing Cells: Skin: Dry Cuticles: Brittle (not the nails because they are dead) Hair: Alopecia Lungs: Shortness of breath, cilia will not clear mucus leading to infections GI: Nausea, Vomiting, Diarrhea (unable to absorb food) Kidneys: PCT will be affected first leading to renal failure Bladder: Oliguria due to urinary retention Vascular Endothelium: Breaks down leading to a vasculitis and vascular bleeding Sperm: Decreased count Breasts: Atrophic Endometrium: Amenorrhea Bone Marrow: Suppressed and all cell counts will be low Germ Cells: Predisposed to Cancer, especially the skin & GI because they are the most rapidly dividing cells Most Common Presenting Signs: Tachypnea and Dyspnea Most Common Presenting Symptoms: Weakness and Shortness of breath Most Common Presenting Infections: Respiratory and Urinary Tract Infections Most Common Cause of Death: Heart Failure

The GABA Connection:

Sowhat happens when you decide to spend your evening at the local bar? You drink some alcohol, and drink some more, and then who knows what happens after that. Why do you have trouble remembering what happened? Its all because of GABA. Increased levels of GABA lead to bradycardia, lethargy, constipation, impotence, and memory loss. This means that anything or any disease that increases acidosis, urea, or ammonia will lead to an increase in GABA. This will slow everything down, leading to a Low Energy State! NH3 + H+ NH4+ + alpha-KetoGlutarate Glutamate GABA

The Neuromuscular Disease State:

These diseases affect all of your muscles to some degree, and the signs and symptoms are due to a global muscular weakness. The characteristics of these diseases are as follows: Most Common Presenting Sign: Tachypnea and Dyspnea Most Common Presenting Symptoms: Weakness and Shortness of Breath Most Common Infections: Respiratory and Urinary Tract Infection Most Common Cause of Death: Respiratory Failure and not heart failure because the cardiac muscle has autonomics.

The Estrogen Connection:

This concept is so simple, but explains so much. The key to understand here is that estrogen is a muscle relaxant. That means that any process where estrogen is increased will mimic a neuromuscular disease state which includes muscle weakness and a low energy state. The only difference is that estrogen does not affect the rapidly dividing cells like the low energy state does. Thus, increased estrogen states (obesity, oral contraceptive use, pregnancy, liver failure, p450 inhibition, etc) will lead to the following: An S3, Vasodilation, Decreased Blood Pressure, Hemorrhoids Constipation, Urinary Retention Reflux, Relaxed Gallbladder Gallstones Decreased risk for Osteoporosis, Colorectal Cancer, and LDL Increased risk for Breast Cancer, Endometrial Cancer, and DVT

Solubility:
Water Soluble: Has a Cell Membrane Destination Is affected by total charge and pH of environment Affected by membrane thickness and surface area Affected by flux and reflection coefficient Is excreted by the Renal System (short drug half-life)

Fat Soluble: Goes right through the cell membrane Usually has a nuclear membrane destination Has a large volume of distribution Is metabolized by the liver (long drug half-life) Is usually hepatotoxic Will affect the brain Membrane diffusion is limited only by a concentration gradient

Pulmonary Disease Concept:

This concept will help you understand 90% of the lung diseases that exist. You could never memorize the blood gas for every known pulmonary pathology out there. But if you can decide whether or not the disease is a restrictive or obstructive process, you can predict their blood gas, chest x-ray, and what they are most likely to die from. So, when you are deciding what type of process it is, ask yourself if they have trouble breathing in or out, and whether they have small stiff lungs or big mucus-filled lungs, then tell me everything you know Restrictive Pattern: These people have a problem in their interstitium and therefore, a problem with oxygenation. They have trouble with breathing in and the hypoxia creates a low energy state Small stiff lungs (Decreased Vital Capacity) FEV1/FVC > 0.8 ABG: Decreased pO2 Decreased pCO2, Increased pH and Respiratory Rate CXR: Reticulo-nodular pattern, ground-glass appearance, or interstitial infiltrate Die of Cor Pulmonale ( hypoxia leads to a low energy state; heart failure due to lung disease is called cor pulmonale) Example: Neuromuscular diseases (breathing out is passive), drugs, autoimmune diseases. Treatment: Give pressure support on ventilator along with Increased O2, Respiratory Rate, and Inspiratory Time. Obstructive Pattern: These people have an airway problem and therefore a problem with ventilation. They have trouble breathing out because there is too much mucus in their airways and goblet cell hyperplasia. FEV1/FVC < 0.8 and Increased Residual Volume Increased Reid Index = Increased Airway Thickness/Airway Lumen ABG: Increased pCO2 Decreased pH and Increased Respiratory Rate Die of Bronchiectasis Example is COPD Treatment is to manipulate rate on the ventilator by increasing the respiratory rate and expiratory time. You only increase O2 if needed. 3

Likeness to Depolarize:
This concept shows you how to predict what the side effects of any electrolyte state would be. For example, hypocalcemia is more likely to depolarize. Thus, they have an overall body state that can be described by the symptoms below. More Likely to Depolarize: Hypocalcemia, Hypomagnesemia, Early Hypernatremia, and Early Hyperkalemia [Opposite of Low Energy State] Brain: Psychosis, Seizures, Jitteriness, Insomnia Skeletal Muscle: spasms, tetany, cramps GI: Diarrhea, then constipation (smooth muscle needs Ca2+ for 2nd messenger system) Cardiac: Tachycardia, arrhythmias

Less Likely to Depolarize: Hypercalcemia, Hypermagnesemia, Early Hyponatremia, and Early Hypokalemia [Think Low Energy State] Brain: Lethargy, mental status changes, depression, delirium, sedation, coma Skeletal Muscle: Weakness, Shortness of breath GI: Constipation, then diarrhea (Na+ to depolarize, the Ca2+-Calmodulin as 2nd messenger system) Cardiac: Hypotension, Bradycardia

The Low Volume State:

This is what happens whenever your body is depleted of volume. Anytime you have chronic low flow to the kidney, a chain of events will occur. Your electrolytes become disorganized, and your body tries to fix itself. This happens in a multitude of disease states such as CHF, vomiting, sweating, aortic stenosis, and anemia. Specifically, you end up with an increase of total body Na+, Decreased serum Na+ (dilutional affect), Decreased serum Cl(dilutional affect), Decreased serum K+(dilutional affect & Net loss), Decreased serum Ca2+ (alkalosis increases Ca2+ Precipitation), Increased pH (due to acid excretion in the collecting duct by aldosterone), and Increased TPR. This is due to the renin-angiotensin-aldosterone system: 1. Low renal blood flow (RBF) leads to low GFR and low creatinine clearance. 2. Low Creatinine Clearance leads to a high serum creatinine. 3. Low RBF leads to release of renin, then higher angiotensin I and II, then higher TPR and higher blood pressure. 4. High Angiotensin-II leads to higher aldosterone, higher sodium reabsorption, and higher total body sodium. 5. Aldosterone reabsorbs sodium in exchange for potassium excretion. It also excretes acid in the collecting duct of the kidneys.

6. The kidney will end up reabsorbing an excess of water in the process. Low Volume States with Acidosis: Diarrhea due to loss of bicarbonate in the small bowel Renal Tubular Acidosis Type 2 due to loss of bicarbonate from the kidney Diabetic Ketoacidosis due to the excess of ketones

The Low Volume State Response:

1. Immediate response is due to the Carotid Sinus (C.S.) Baroreceptor a. Increases sympathetic discharge leading to a high heart rate (reflex tachycardia) b. The carotid sinus baroreceptor responds to stretch (volume) leading to the regulation of blood pressure. c. A Decrease in Stroke Volume Decrease in Stretch Carotid Sinus Decrease firing of Cranial Nerve 9 (afferent) Decrease firing of Cranial Nerve 10 (efferent) Increase in Sympathetic Discharge Increase in Heart Rate and Blood Pressure. d. Thus, Stoke Volume (Stretch) goes the same direction as the firing of Cranial Nerves 9 & 10. i. Ways to Increase Stroke Volume 1. Rub carotid sinus 2. Vaso-vagal response (cough, sneeze, urinate) replicate with the tilt test. ii. Ways to Decrease Stroke Volume 1. Tonsillectomy (by cutting Cranial Nerve 9) 2. Nitrate use for angina (give beta-blockers first for MI patients to protect the heart) 3. When you stand up, (the Systolic Blood Pressure decreases by 5-10 mm Hg and Pulse increases by 5-10 beats/minute.) a. If pulse goes up > 10 bpm Hypovolemia CO = HR (pulse) x SV (blood pressure) 1. Early Shock: the pulse increases greater than 10 bpm when standing up (orthostatic hypotension = compensated shock). 2. Late Shock: Blood Pressure decreases greater than 10 mm Hg when standing up (uncompensated leading to a low Cardiac Output). b. If pulse goes up < 5 bpm Autonomic Dysfunction (stand up and pass out without warning) i. Babies: Riley-Day Syndrome ii. Adults: Diabetes Mellitus (infarcts C.S.)

2.

iii. Elderly: Sick Sinus Syndrome iv. Parkinsons: Shy-Dragger Syndrome Intermediate response is due to the Medulla a. The nucleus tractus solitarius signals the release of norepinephrine. b. The norepinephrine release has a higher affinity for alpha receptors. c. The vessels vasoconstrict d. This leads to Increased Heart Rate and Blood Pressure Long-Term response is due to the Kidney a. The norepinephrine release also vasoconstricts the renal blood supply. b. The JG-apparatus in the afferent arteriole of the kidney responds to flow and volume. c. The low RBF signals the JG-apparatus to release renin which leads to i. High Total Peripheral Resistance (TPR) ii. Increase Sodium Reabsorption iii. Increase Potassium Excretion leading to alkalosis iv. Increase water reabsorption leads to a dilutional decrease in serum sodium, chloride, and potassium. d. Physiological response to fixing the pressure: JG-apparatus releases renin Liver (angiotensinogen) AT-I Lungs (ACE) AT-II (very potent vasoconstrictor) to the efferent more than afferent arterioles in order to re-establish GFR Increase TPR Increase Blood Pressure. e. Physiological response to fixing the volume: AT-II Aldosterone Na+/K+ pumps in kidney DCT Increase Na+ reabsorption Increase total body water Drags in 3 molecules of water with each molecule of Na+ Decreases serum Na+ serum K+ decreases (secretion) Aldosterone also secretes H+ Increases pH.

3.

Acute Renal Failure:

Can be oliguric (decreased urine output) or anuric (no urine output at all) 1. Pre-Renal a. This means low RBF to the kidney; low volume state applies here b. Labs: i. BUN/Creatinine Ratio greater than 20:1 ii. FeNa+ below 1% (normal is 1-10%) iii. Urine Na+ below 10 (normal is 10-20) Renal a. This means damage to the glomerulus or to the nephron b. Things that are normally reabsorbed will no longer be reabsorbed and will therefore be low in the serum. c. Things that are normally secreted will no longer be secreted and will therefore be elevated in the serum. d. Labs: i. Increase in BUN/Creatinine Ratio, but less than 20:1 6

2.

3.

ii. FeNa+ is greater than 10% iii. Urine Na+ is greater than 10 Post-Renal a. This means that there is an obstruction somewhere after the collecting ducts. b. The patient usually presents with anuria rather than oliguria. c. There is also a weak urinary stream, dribbling, urgency after urinating and sometimes, overflow incontinence.

Renal Pattern:
Nephritic Syndrome: Essentially, this means that the fenestrations are larger than they should be, but the basement membrane negative charge is still intact. Every vasculitis will lead to a nephritic pattern. Characteristics: 1. Hematuria (brown urine) 2. Hypertension 3. Oliguria 4. Edema and Generalized Fluid Retention Nephrotic Syndrome: Essentially, this means that the basement membrane negative charge has been impaired by the deposition of something. This is the reason why albumin leaks out freely (loss of proteins > 3.5 grams/24 hours) leading to Hypoalbuminemia (Less than 30 grams/dL). This will then lead to edema and frothy urine. This then prompts the liver to try to compensate for the loss of proteins by making lipoproteins (which lead to hyperlipidemia and hypercholesterolemia) as well as clotting factors (leading to a hypercoagulable state). There can either be intravascular volume depletion with hypotension or intravascular volume expansion with hypertension, depending on the stage of the pathology.

Acute vs. Chronic Disease Pattern:

How many times have you wondered what kind of cells would show up on histology for any given syndrome? All you need to understand is that the inflammatory response is the same for all diseases, and happen on a timeline. This means that the acute diseases will have swelling and increased neutrophils (PMNs), whereas chronic diseases will have fibroblasts or fibrosis. The Inflammatory Response Timeline is as follows: 1. Less than 24 hours: Swelling 2. Day 1: PMNs show up at 24 hours 3. Day 3: PMNs peak 4. Day 4: Macrophages and T-Cells show up

5. Day 7: Macrophages and T-Cells peak, then Fibroblasts show up 6. Day 30: Fibroblasts Peak 7. Month 3-6: Fibroblasts leave and Fibrosis is complete.

The Two Arms of the Immune Response:

We all know that there are two arms of the immune response, the humoral and cellmediated. However, if you can decide whether a disease is humoral or cell-mediated, you can predict what type of cells will be found there, what type of culture you should order, and whether an antibiotic is going to help or not. So ask yourself this question: Are Bcells and PMNs involved or T-cells and Macrophages? If you dont know that, is bacterial involved or not? If bacteria are not involved, just follow the most common list of cell-mediated killers listed in the most common order of occurrence from viruses to fungi and down Humoral Immune Response: Patrols: o Blood o Do Culture Policemen: o B-Cells o PMNs o TH2 The Bad Guys: o Bacteria Cell Mediated Immune Response: Nutrition affects here first Patrols: o Tissue o Do Biopsy Policemen: o T-Cells o Macrophages Blood: Monocytes Brain: Microglia Lung: Type I Pneumocytes Liver: Kupfer cells Spleen: RES cells Lymph: Dendritic cells Kidney: Mesangial cells Peyers Patches: M-cells Skin: Langerhans Bone: Osteoclasts

Connective Tissue: Histiocytes Giant cells Epithelioid cells

The Bad Guys: o Virus (CMV, EBV is most common) o Fungi o Mycobacterium o Protozoa kills you o Parasite o Neoplasm

Vasculitis:
We all know that -it is means there is an inflammatory process, right? So the white blood cell (WBC) count is going to be high. However, this is not a bacterial process which means it has to be cell-mediated, which will have high levels of T-Cells and Macrophages. Now, these cells are going to be ripping red blood cells (RBC) and platelets, and you will see schistocytes in the peripheral blood smear. Now you know the CBC for every vasculitis: 1. Increased WBC count due to inflammation 2. Increased T-Cells and Macrophages since it is cell-mediated inflammation 3. Decreased RBC and Platelet count due to destruction 4. Increased Eosinophil count for Collagen Vascular Diseases Just to tie this in You have a vasculitis, and your RBC is low. What do you need RBC for? You need it for oxygen. What do you need oxygen for? You need it for making energy. So what state are we in when there is a vasculitis? You are in the Low Energy State and you know what happens in that! Pulmonary and Cardiac Manifestations: Hypoxia constricts the pulmonary vessels Increased Resistance and Pressure Pulmonary Hypertension Narrowing of S2 Increase of the S2 Intensity Right Ventricular Hypertrophy an S4 increases on Inspiration Then an Increase in Central Venous Pressure (CVP). Renal Manifestations: Recall that all vasculitides lead to a Nephritic Syndrome Pattern. When a blood vessel tears CLOT FORMATION Decrease radius of the vessel Increased Resistance Increased Blood Pressure. Also recall that Decreased Flow to the Kidney is Ischemia. Here are the seven patterns in the kidney for vasculitis: A partial clot in the renal artery Renal Artery Stenosis Complete clot in the renal artery Renal Failure An inflamed glomerulus Glomerular-Nephritis 9

Complete clot of the renal medulla Interstitial Nephritis Complete clot of the renal papilla Papillary Necrosis A partial clot of the renal nephron Focal Segmental Glomerulus Nephritis Complete clot of the renal nephron Rapid Progressive Glomerulo-Nephritis

10