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 Estrogen Connection:
This concept is so simple. This means that anything or any disease that increases acidosis. Increased levels of GABA lead to bradycardia. The key to understand here is that estrogen is a muscle relaxant. but explains so much. Relaxed Gallbladder Gallstones Decreased risk for Osteoporosis. or ammonia will lead to an increase in GABA. and memory loss. Why do you have trouble remembering what happened? It’s all because of GABA. Hemorrhoids Constipation. Thus. The only difference is that estrogen does not affect the rapidly dividing cells like the low energy state does. Vasodilation. and LDL Increased risk for Breast Cancer. 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. Urinary Retention Reflux. oral contraceptive use. Colorectal Cancer. etc) will lead to the following: • • • • • An S3. p450 inhibition. liver failure. This will slow everything down. increased estrogen states (obesity. constipation. That means that any process where estrogen is increased will mimic a neuromuscular disease state which includes muscle weakness and a low energy state. impotence. and then who knows what happens after that.The GABA Connection:
So…what happens when you decide to spend your evening at the local bar? You drink some alcohol. urea. pregnancy. Endometrial Cancer. and drink some more. Decreased Blood Pressure. 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 DVT
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)
. lethargy. and the signs and symptoms are due to a global muscular weakness.
You could never memorize the blood gas for every known pulmonary pathology out there. a problem with oxygenation. then tell me everything you know… Restrictive Pattern: • These people have a problem in their interstitium and therefore. and Inspiratory Time. 3
. you can predict their blood gas. drugs. • FEV1/FVC < 0. Increased pH and Respiratory Rate • CXR: Reticulo-nodular pattern. • 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. and whether they have small stiff lungs or big mucus-filled lungs. Obstructive Pattern: • These people have an airway problem and therefore a problem with ventilation. So. Respiratory Rate. or interstitial infiltrate • Die of Cor Pulmonale ( hypoxia leads to a low energy state.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. chest x-ray. and what they are most likely to die from. when you are deciding what type of process it is. autoimmune diseases. But if you can decide whether or not the disease is a restrictive or obstructive process. ground-glass appearance. heart failure due to lung disease is called cor pulmonale) • Example: Neuromuscular diseases (breathing out is passive). You only increase O2 if needed.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. • Treatment: Give pressure support on ventilator along with Increased O2. • They have trouble breathing out because there is too much mucus in their airways and goblet cell hyperplasia. ask yourself if they have trouble breathing in or out.
Early Hyponatremia. and Early Hyperkalemia [Opposite of Low Energy State] • • • • Brain: Psychosis. sweating. sedation. then diarrhea (Na+ to depolarize. 5. Insomnia Skeletal Muscle: spasms. depression. and higher total body sodium.Likeness to Depolarize:
This concept shows you how to predict what the side effects of any electrolyte state would be. a chain of events will occur. High Angiotensin-II leads to higher aldosterone. aortic stenosis. Hypermagnesemia. higher sodium reabsorption. Decreased serum Ca2+ (alkalosis increases Ca2+ Precipitation). 4. 3. the Ca2+-Calmodulin as 2nd messenger system) Cardiac: Hypotension. then higher angiotensin I and II. mental status changes.
. coma Skeletal Muscle: Weakness. This happens in a multitude of disease states such as CHF. you end up with an increase of total body Na+. then higher TPR and higher blood pressure. Seizures. Your electrolytes become disorganized. More Likely to Depolarize: Hypocalcemia. Aldosterone reabsorbs sodium in exchange for potassium excretion. Decreased serum Na+ (dilutional affect). 2. Decreased serum Cl–(dilutional affect). and anemia. For example. Specifically. and Early Hypokalemia [Think Low Energy State] • • • • Brain: Lethargy. vomiting. arrhythmias
Less Likely to Depolarize: Hypercalcemia. Anytime you have chronic low flow to the kidney. delirium. hypocalcemia is more likely to depolarize. Shortness of breath GI: Constipation. Low renal blood flow (RBF) leads to low GFR and low creatinine clearance. Bradycardia
The Low Volume State:
This is what happens whenever your body is depleted of volume. and Increased TPR. Hypomagnesemia. and your body tries to fix itself. Low Creatinine Clearance leads to a high serum creatinine. then constipation (smooth muscle needs Ca2+ for 2nd messenger system) Cardiac: Tachycardia. This is due to the renin-angiotensin-aldosterone system: 1. Thus. Jitteriness. Decreased serum K+(dilutional affect & Net loss). they have an overall body state that can be described by the symptoms below. cramps GI: Diarrhea. Low RBF leads to release of renin. tetany. Increased pH (due to acid excretion in the collecting duct by aldosterone). It also excretes acid in the collecting duct of the kidneys. Early Hypernatremia.
d. b. Increases sympathetic discharge leading to a high heart rate (reflex tachycardia) b.) Baroreceptor a.)
. Late Shock: Blood Pressure decreases greater than 10 mm Hg when standing up (uncompensated leading to a low Cardiac Output). The carotid sinus baroreceptor responds to stretch (volume) leading to the regulation of blood pressure. Thus.S. c. i. Stoke Volume (Stretch) goes the same direction as the firing of Cranial Nerves 9 & 10. If pulse goes up < 5 bpm Autonomic Dysfunction (stand up and pass out without warning) i. 2. Adults: Diabetes Mellitus (infarcts C.S. Tonsillectomy (by cutting Cranial Nerve 9) 2. ii. sneeze. The kidney will end up reabsorbing an excess of water in the process.) a. urinate) replicate with the tilt test. Vaso-vagal response (cough. 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. When you stand up. If pulse goes up > 10 bpm Hypovolemia • CO = HR (pulse) x SV (blood pressure) 1. Rub carotid sinus 2. Ways to Increase Stroke Volume 1. 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. Babies: Riley-Day Syndrome ii. Immediate response is due to the Carotid Sinus (C. Nitrate use for angina (give beta-blockers first for MI patients to protect the heart) 3. Early Shock: the pulse increases greater than 10 bpm when standing up (orthostatic hypotension = compensated shock). Ways to Decrease Stroke Volume 1. (the Systolic Blood Pressure decreases by 5-10 mm Hg and Pulse increases by 5-10 beats/minute.6.
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. BUN/Creatinine Ratio greater than 20:1 ii. e. c. The vessels vasoconstrict d. FeNa+ below 1% (normal is 1-10%) iii. chloride.
iii. Elderly: Sick Sinus Syndrome iv. low volume state applies here b. Labs: i. Increase water reabsorption leads to a dilutional decrease in serum sodium. Things that are normally reabsorbed will no longer be reabsorbed and will therefore be low in the serum. The nucleus tractus solitarius signals the release of norepinephrine. The JG-apparatus in the afferent arteriole of the kidney responds to flow and volume. Labs: i. c. Pre-Renal a. Increase in BUN/Creatinine Ratio. The norepinephrine release has a higher affinity for alpha receptors. c. but less than 20:1 6
2. Increase Sodium Reabsorption iii. High Total Peripheral Resistance (TPR) ii. Parkinson’s: Shy-Dragger Syndrome Intermediate response is due to the Medulla a. This leads to Increased Heart Rate and Blood Pressure Long-Term response is due to the Kidney a. b.
Acute Renal Failure:
Can be oliguric (decreased urine output) or anuric (no urine output at all) 1. d. Increase Potassium Excretion leading to alkalosis iv. Urine Na+ below 10 (normal is 10-20) Renal a. The low RBF signals the JG-apparatus to release renin which leads to i. b. The norepinephrine release also vasoconstricts the renal blood supply. and potassium. Things that are normally secreted will no longer be secreted and will therefore be elevated in the serum. d. 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. This means low RBF to the kidney.2.
3. This means damage to the glomerulus or to the nephron b.
whereas chronic diseases will have fibroblasts or fibrosis. • 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). 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. Day 1: PMNs show up at 24 hours 3. This means that there is an obstruction somewhere after the collecting ducts. FeNa+ is greater than 10% iii. The patient usually presents with anuria rather than oliguria. this means that the fenestrations are larger than they should be. The Inflammatory Response Timeline is as follows: 1. There is also a weak urinary stream. Day 3: PMNs peak 4. Hematuria (brown urine) 2. • There can either be intravascular volume depletion with hypotension or intravascular volume expansion with hypertension.
Acute vs. this means that the basement membrane negative charge has been impaired by the deposition of something. depending on the stage of the pathology.
ii. dribbling. and happen on a timeline.5 grams/24 hours) leading to Hypoalbuminemia (Less than 30 grams/dL).3.
Nephritic Syndrome: • Essentially. Less than 24 hours: Swelling 2. This means that the acute diseases will have swelling and increased neutrophils (PMNs). • Every vasculitis will lead to a nephritic pattern. Oliguria 4. b. • This is the reason why albumin leaks out freely (loss of proteins > 3. c. Day 4: Macrophages and T-Cells show up
. but the basement membrane negative charge is still intact. Hypertension 3. Edema and Generalized Fluid Retention Nephrotic Syndrome: • Essentially. urgency after urinating and sometimes. overflow incontinence. Urine Na+ is greater than 10 Post-Renal a. • Characteristics: 1. • This will then lead to edema and frothy urine.
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 Peyer’s Patches: M-cells Skin: Langerhans Bone: Osteoclasts
. then Fibroblasts show up 6.5. Day 7: Macrophages and T-Cells peak. if you can decide whether a disease is humoral or cell-mediated. Month 3-6: Fibroblasts leave and Fibrosis is complete. and whether an antibiotic is going to help or not. the humoral and cellmediated. However. what type of culture you should order. is bacterial involved or not? If bacteria are not involved.
The Two Arms of the Immune Response:
We all know that there are two arms of the immune response. So ask yourself this question: Are Bcells and PMNs involved or T-cells and Macrophages? If you don’t know that. Day 30: Fibroblasts Peak 7. you can predict what type of cells will be found there.
and you will see schistocytes in the peripheral blood smear. When a blood vessel tears CLOT FORMATION Decrease radius of the vessel Increased Resistance Increased Blood Pressure. Increased T-Cells and Macrophages since it is cell-mediated inflammation 3. Also recall that Decreased Flow to the Kidney is Ischemia. 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). these cells are going to be ripping red blood cells (RBC) and platelets. right? So the white blood cell (WBC) count is going to be high. What do you need oxygen for? You need it for making energy. which will have high levels of T-Cells and Macrophages. and your RBC is low. Increased WBC count due to inflammation 2. Increased Eosinophil count for Collagen Vascular Diseases Just to tie this in… You have a vasculitis. Decreased RBC and Platelet count due to destruction 4. However.
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
We all know that “-it is” means there is an inflammatory process. this is not a bacterial process – which means it has to be cell-mediated. What do you need RBC for? You need it for oxygen. Now you know the CBC for every vasculitis: 1. Now. Renal Manifestations: Recall that all vasculitides lead to a Nephritic Syndrome Pattern. 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