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The Complete Guide to Differential Diagnoses

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Sam Gharbi
Sam Gharbi

The differential diagnosis is at the core of medicine. Without a good differential to start off with, your approach to the history, physical, and investigations will be incomplete. In essence, your entire assessment of the patient begins with your differential diagnosis in regards to the presenting complaint. This document started as notes that I had made for myself over the years during the course of my medical training, and ultimately has evolved into an e-book that is a collection of differential diagnoses that address a variety of medical problems. The differentials outlined in this e-book cover the topic of internal medicine, although are generally applicable to most fields of medicine. Topic exclusions notably include obs/gyn, pediatrics, and psychiatry, as they are unfortunately outside the scope of my expertise and practice. Ultimately this e-book is meant to be a user friendly educational guide with the purpose of bestowing a general framework for medical learners. It is not meant to be a clinical reference guide to be used for medical decision making, nor is it meant to be a complete list of every different possible pathology that may be contributing to a differential diagnosis

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Sam Gharbi, MD Understanding Internal Medicine A complete Guide to Differential Diagnoses
written by Sam Gharbi, MD Understanding Internal Medicine Differential Diagnoses
2 Disclaimer Extensive effort has been exerted in order to make this book as accurate as possible. However, the accuracy and completeness of the information provided cannot be guaranteed. This book is to be used as an educational guide only, and healthcare professionals should use sound clinical judgement and individualize therapy to each specific patient care situation. The author makes no claims whatsoever, expressed or implied, about the authenticity, accuracy, reliability, com- pleteness, or timeliness of the material presented in this book. In no event shall the author be liable to any party for indirect, direct, special, incidental, or consequential damages, including but not limited to lost profits arising out of the use of this book, even if the author has been advised of such damage. By having read the above, or by use of this book, be it partially or in its entirety, you have explicitly consented your agreement to the above disclaimer.
3 © Copyright 2013 Sam Gharbi. All Rights Reserved.
4 INTRODUCTION The differential diagnosis is at the core of medicine. Without a good differential to start off with, your approach to the history, physical, and investigations will be incomplete. In essence, your entire assessment of the patient begins with your differential diagnosis in regards to the presenting complaint. This document started as notes that I had made for myself over the years during the course of my medical training, and ulti- mately has evolved into an e-book that is a collection of differential diagnoses that address a variety of medical problems. The differentials outlined in this e-book cover the topic of internal medicine, although are generally applicable to most fields of medi- cine. Topic exclusions notably include obs/gyn, pediatrics, and psychiatry, as they are unfortunately outside the scope of my ex- pertise and practice. Ultimately this e-book is meant to be a user friendly educational guide with the purpose of bestowing a general framework for medical learners. It is not meant to be a clinical reference guide to be used for medical decision making, nor is it meant to be a complete list of every different possible pathology that may be contributing to a differential diagnosis. I hope that you, the reader, find this e-book to be a helpful educational resource. Sincerely, Sam Gharbi Internal Medicine Physician MD, CM, FRCPC
5 Please feel free to click on the icon below which will enable you to anonymously message me with feedback regarding the e-book & how it can be further improved. Your feedback is greatly appreciated. FEEDBACK
6 Click on the icon below to take notes & save them within this e-book MY NOTES
On history: • Chest pain…………………………………. • Syncope…………………………………… • Palpitations……………………………….. On physical: • Hypertension……………………………..... • Hypotension/Shock………………………... • Bradycardia/Tachycardia............................... • Abnormal Heart Sounds............................... • Peripheral Edema……………………......... On labs: • Elevated Troponins………………………............ On ECG: • T Wave Inversions/ST changes................... • Tachyarrhythmias………………………… • Conduction Block………………………… • Bundle Branch Block…………………….. • Prolonged QT Segment…………………… Overview of Topics Chapter 1 Cardiology Reviewed by Dr. Richard Vandegriend
DDx of Chest PainDDx of Chest Pain Cardiac • Coronary Artery Disease • Acute Coronary Syndromes (Myocardial Infarct) • Aortic Dissection • Myopericarditis Pulmonary • Pneumonia • Pulmonary Embolism • Pneumothorax • Pleuritis • Pulmonary Hypertension GI • Gastroesophageal reflux disease (GERD) • Esophagitis • Esophageal spasm • Esophageal dissection (Mallory Weiss syndrome) • Esophageal rupture (Boerhave’s syndrome) • Peptic Ulcer Disease • Biliary Disease • Pancreatitis Musculoskeletal • Costochondritis • Osteoarthritis Other • Herpes zoster • Anxiety 8 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Chest Pain ____________________________________________________________________________________________________________________________________________________________________ The Short List - Chest Pain 1. Coronary Artery Disease (CAD) 2. Acute Coronary Syndrome (ACS) 3. Aortic Dissection 4. Pericarditis 5. Gastroesophageal reflux disease (GERD) 6. Costochondritis On history
DDx of SyncopeDDx of Syncope Cardiovascular (Cardiogenic) • Arrhythmia • Valvular heart disease (particularly AS & MS) • Hypertrophic cardiomyopathy • Pericardial tamponade • Pulmonary embolism • Pulmonary hypertension Neurologic (Neurogenic) • Seizure (technically not syncope) • TIA/Stroke Neurocardiogenic • Vasovagal syncope • Carotid sinus hypersensitivity • Situational syncope (cough, deglutition, defecation, & micturition syncope) Orthostatic • Hypovolemia • Drug induced • Autonomic neuropathy (from diabetes, alcohol, renal failure, Parkinson’s & amyloidosis) Other (technically not syncope) • Hypoglycemia • Anemia • Hypoxia • Psychogenic 9 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Syncope ____________________________________________________________________________________________________________________________________________________________________ The Short List - Syncope 1. Arrhythmia 2. Aortic Stenosis 3. TIA/Stroke 4. Vasovagal syncope 5. Orthostatic hypotension 6. Hypoglycemia On history
DDx of PalpitationsDDx of Palpitations Cardiac • Premature Ventricular Contractions (PVCs) • Premature Atrial Contractions (PACs) • Any Tachyarrhythmia • Pacemaker Endocrine • Hyperthyroidism • Hypoglycemia • Pheochromocytoma Drugs Prescription Drugs: • Sympathomimetics • Anticholinergics • Beta blocker withdrawal Other Drugs: • Nicotine • Caffeine • Cocaine • Amphetamines Psychiatric • Panic attack • Generalized anxiety disorder • Depression • Somatization Other • Stress • Exercise • Fever • Anemia • Pregnancy 10 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Palpitations ____________________________________________________________________________________________________________________________________________________________________ The Short List - Palpitations 1. Premature Ventricular Contractions (PVCs) 2. Tachyarrhythmias (ie. AFib, AFlutter, SVT) 3. Hyperthyroidism 4. Hypoglycemia 5. Drugs 6. Panic Attacks On history
DDx of HypertensionDDx of Hypertension Renal • Renal parenchymal disease o Chronic kidney disease o Glomerulonephritis o Polycystic kidney disease • Renovascular disease o Renal artery stenosis Endocrine • Hypo and Hyperthyroidism • Hypercalcemia • Hyperaldosteronism • Cushing’s disease • Pheochromocytoma Drugs Medical Drugs: • Oral contraceptives (OCPs) • NSAIDS • Steroids Illicit Drugs: • Chronic alcohol use & withdrawal • Cocaine • Amphetamines Other • Obstructive sleep apnea (OSA) • Coarctation of the aorta • Polycythemia vera • Pre-eclampsia & eclampsia 11 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Hypertension ____________________________________________________________________________________________________________________________________________________________________ The Short List - Hypertension 1. Essential Hypertension (most common) 2. Chronic kidney disease 3. Thyroid disease 4. Hypercalcemia 5. Drugs - OCPs/NSAIDs/Steroids 6. OSA Hypertension Workup • Routine workup for hypertension often involves bloodwork, including CBC, electrolytes, creatinine & BUN, as well as ECG and chest X-ray • In patients suspected of having a secondary cause of hypertension, depend- ing on history and physical findings, further workup may involve any of the following: o TSH o Serum calcium o Plasma Aldosterone to Renin ratio (for hyperaldosteronism) o 24 hour urine catecholamines (for pheochromocytoma) o Urinalysis (looking for proteinuria or casts in glomerulonephritis) o Overnight oximetry (for OSA) On physical
______________________________________________________________________________ Hypertension + Tachycardia ______________________________________________________________________________ DDx of HTN + TachycardiaDDx of HTN + Tachycardia Endocrine • Thyrotoxicosis • Pheochromocytoma Drugs • Alcohol withdrawal • Cocaine/Amphetamine toxicity Other • Neuroleptic Malignant Syndrome (NMS) • Malignant Hyperthermia • Serotonin Syndrome ______________________________________________________________________________ Hypotension/Shock ______________________________________________________________________________ 12 Cardiology NOTE: The differential diagnosis for hypotension is almost identical to that of shock, except for the fact that drugs (both medical and illicit) are a major contributor in the case of hypotension but rarely cause shock unless in cases of overdose. On physical DDx of Hypotension/ShockDDx of Hypotension/Shock Hypovolemic • Hemorrhage • GI tract loss (vomiting, diarrhea) • Urinary tract loss (diabetes insipidus) • Third spacing (pancreatitis, bowel obstruction) • Skin loss (severe burns) Cardiogenic • Acute myocardial infarct & its complications • End-stage cardiomyopathy • Hypertrophic obstructive cardiomyopathy (HOCM) • Severe valvular dysfunction Obstructive • Cardiac tamponade • Massive pulmonary embolism • Tension pneumothorax • Cor pulmonale Distributive • Septic shock • Anaphylactic shock • Neurogenic shock • Adrenal crisis or adrenal insufficiency Drugs • Any BP lowering agent (ie. beta blockers, CCBs)
________________________________________________________________________ Bradycardia ________________________________________________________________________ DDx of BradycardiaDDx of Bradycardia Cardiac • Bradyarrhythmias o Sinus Bradycardia o Sick Sinus Syndrome • Conduction block • Myocardial Infarct Drugs • Beta blockers • Calcium channel blockers • Digoxin • Antiarrhythmic drugs Endocrine • Hypothyroidism • Hypothermia Metabolic • Hyperkalemia • Hypokalemia Infiltrative • Sarcoidosis • Amyloidosis • Hemochromatosis Infectious • Endocarditis ________________________________________________________________________ Sinus Tachycardia ________________________________________________________________________ DDx of Sinus TachycardiaDDx of Sinus Tachycardia Cardiac • Myocardial infarction • Congestive Heart failure Pulmonary • Pulmonary Embolism • Chronic pulmonary disease • Hypoxia Endocrine • Hyperthyroidism • Pheochromocytoma Drugs • Beta-agonists (ie. ventolin) • Alcohol withdrawal • Nicotine • Caffeine • Cocaine • Amphetamines Psychiatric • Panic attacks • Generalized anxiety disorder Other • Pain • Fever • Sepsis • Hypovolemia • Hypotension and shock • Anemia • Postural Tachycardia Syndrome (POTS) 13 Cardiology On physical
________________________________________________________________________ Abnormal Heart Sounds - S1 & S2 ________________________________________________________________________ DDx of Abnormal Heart SoundsDDx of Abnormal Heart Sounds Loud S1 • Mitral stenosis • Tricuspid stenosis • Mitral valve prolapse (MVP) • Atrial & Ventricular septal defects • Atrial myxoma • Tachycardia • Short PR interval Soft S1 • Severe Mitral stenosis • Mitral regurgitation • Aortic regurgitation (acute) • Aortic stenosis (severe) • Dilated cardiomyopathy • Left bundle branch block (LBBB) • Long PR interval Fixed splitting of S2 • Atrial septal defect • Severe right ventricular failure Paradoxical splitting of S2 Prolonged left ventricular ejection time: • Aortic stenosis • Aortic regurgitation • Myocardial infarct • Hypertension • Hypertrophic obstructive cardiomyopahty Delayed left ventricular activation: • Left bundle branch block • Wolffe-Parkinson-White syndrome ________________________________________________________________________ Abnormal Heart Sounds - S3 & S4 ________________________________________________________________________ DDx of Abnormal Heart SoundsDDx of Abnormal Heart Sounds S3 gallop • Congestive Heart Failure • Mitral regurgitation • Tricuspid regurgitation • Aortic regurgitation • Thyrotoxicosis • Pregnancy S4 gallop • Aortic Stenosis • Myocardial infarct (during acute phase) • Hypertension • Hypertrophic cardiomyopathy • Pulmonary Hypertension 14 Cardiology On physical
________________________________________________________________________ Bilateral Peripheral Edema ________________________________________________ DDx of Bilateral Peripheral EdemaDDx of Bilateral Peripheral Edema Increased capillary hydraulic pressure • Congestive Heart Failure (CHF) • Pregnancy • Drugs: o NSAIDs o Calcium Channel Blockers o Estrogens (OCPs, HRT) Hypoalbuminemia • Nephrotic syndrome • Cirrhosis • Malnutrition • Protein-losing enteropathy (ie. colitis) Endocrine disease • Hypothyroidism • Grave’s disease ________________________________________________________________________ Unilateral Peripheral Edema ________________________________________________ DDx of Unilateral Peripheral EdemaDDx of Unilateral Peripheral Edema Increased capillary permeability • Trauma (muscle strain, tear, or injury) • Ruptured Baker’s cyst (popliteal cyst) • Cellulitis • Arthritis • Allergic reactions • Burns Increased interstitial oncotic pressure • Deep vein thrombosis (DVT) • Venous insufficiency • Lymphedema/Lymphatic obstruction 15 Cardiology On physical
DDx of Elevated TroponinsDDx of Elevated Troponins Cardiac • Myocardial infarct • Myocarditis • Endocarditis • Aortic Dissection • Congestive heart failure • Aortic stenosis • Cardioversion • Cardiac trauma • Other cardiomyopathy Pulmonary • Pulmonary embolism • Pulmonary hypertension Renal • Renal failure • Hemodialysis Infiltrative • Sarcoidosis • Amyloidosis • Hemochromatosis Other • Sepsis • Stroke • Subarachnoid hemorrhage 16 Cardiology Notes Troponins originate from heart muscle, and elevated levels often indicate underly- ing damage to cardiac tissue in the form of ischemia or infarct. Overall, there are 3 underlying mechanisms for an elevation in troponins: 1. Primary myocardial infarct • This is usually in the form of underlying atherosclerosis and/or plaque rupture 2. Secondary myocardial infarct • This is in the form of supply-demand mismatches from systemic causes such as hypertensive emergency or anemia 3. Heart Strain • This is actually not infarct, but cardiac strain causing release of troponins. The rise in troponins is usually less marked in these situations, such as CHF, sepsis, intracranial hemorrhage, etc. On labs __________________________________________________________________________________________________________________________________________________________________ Elevated Troponins __________________________________________________________________________________________________________________________________________________________________ The Short List - Elevated Troponins • Myocardial Infarct • Myocarditis • Aortic Dissection • Pulmonary embolism • Renal failure • Sepsis
________________________________________________________________________ T Wave Inversions ________________________________________________________________________ DDx of Ischemic ECG ChangesDDx of Ischemic ECG Changes T wave inversion Cardiac etiologies: • Myocardial ischemia or infarct • Cardiomyopathy • Mitral Valve prolapse • Ventricular hypertrophy • Bundle Branch Block • Post-tachycardia Other etiologies: • Intracranial bleed • Digoxin toxicity • Electrolyte abnormalities (ie. Hypokalemia) ________________________________________________________________________ ST Segment Changes ________________________________________________________________________ DDx of Ischemic ECG ChangesDDx of Ischemic ECG Changes ST depression Cardiac etiologies: • NSTEMI • Posterior STEMI (ST depression in V1-V2) • Post-MI • Ventricle Hypertrophy with strain • Bundle Branch Block • Wolff-Parkinson-White syndrome Other etiologies: • Digoxin effect (scooping) • Hypokalemia • Hypomagnesemia ST elevation Cardiac etiologies: • STEMI • LV aneurysm • Left Bundle Branch Block • Coronary Spasms (Prinzmetal’s Angina) • Pericarditis • Myocarditis Other etiologies: • Pulmonary embolism • Hypothermia 17 Cardiology On ECG
18 Cardiology __________________________________________________________________________________________________________________________________________________________________ Tachyarrhythmias - Narrow Complex (QRS <120ms) __________________________________________________________________________________________________________________________________________________________________ On ECG DDx of Narrow Complex Tachyarrhythmias (QRS < 120 ms)DDx of Narrow Complex Tachyarrhythmias (QRS < 120 ms) Regular rhythm With P Waves: • Sinus Tachycardia • Atrial Tachycardia • Atrial Flutter • AVRT Without P Waves: • AVNRT Irregular rhythm With P Waves: • Atrial Tachycardia with variable block • Atrial Flutter with variable block • Multifocal Atrial Tachycardia (MAT) Without P Waves: • Atrial Fibrillation Narrow Complex Tachyarrhythmias (QRS<120 ms) With P waves • Sinus Tachycardia • Atrial Flutter • AVRT Without P waves • AVNRT Regular Rhythm Irregular Rhythm With P waves • Atrial Flutter with variable block • Multifocal Atrial Tachycardia (MAT) Without P waves • Atrial Fibrillation
19 Cardiology On ECG __________________________________________________________________________________________________________________________________________________________________ Tachyarrhythmias - Wide Complex (QRS >120 ms) __________________________________________________________________________________________________________________________________________________________________ DDx of Wide Complex Tachyarrhythmias (QRS >120 ms)DDx of Wide Complex Tachyarrhythmias (QRS >120 ms) Regular rhythm • Ventricular Tachycardia • SVT with aberrancy • Pacemaker arrhythmia • Artifact Irregular rhythm • Ventricular Fibrillation • Atrial Fibrillation with aberrancy Wide Complex Tachyarrhythmias (QRS>120 ms) Regular Rhythm Irregular Rhythm • Ventricular Tachycardia • SVT with aberrancy • Pacemaker arrhythmia • Artifact • Ventricular Fibrillation • Atrial Fibrillation with aberrancy
DDx of Conduction BlockDDx of Conduction Block Cardiac • Coronary artery disease • Acute coronary syndrome (myocardial infarct) • Cardiomyopathy • Myocarditis • Endocarditis • Increased vagal tone • Congenital heart disease Metabolic • Hyperkalemia • Hypo or Hyperthyroidism Drugs • Beta blocker • Calcium channel blocker • Digoxin • Amiodarone Infiltrative • Infiltrative malignancy (ie. lymphoma) • Amyloidosis • Sarcoidosis • Tuberculosis Iatrogenic • Cardiac surgery • Catheter ablation 20 Cardiology On ECG __________________________________________________________________________________________________________________________________________________________________ Conduction Block (AV block) __________________________________________________________________________________________________________________________________________________________________ The Short List - Conduction Block • Coronary artery disease • Myocardial infarct • Cardiomyopathy • Congenital heart disease • Drugs
________________________________________________________________________ Right Bundle Branch Block ________________________________________________________________________ DDx of Right Bundle Branch BlockDDx of Right Bundle Branch Block Cardiac • Coronary artery disease • Myocardial infarct • Right heart failure (cor pulmonale) • Myocarditis • Cardiomyopathies • Hypertension Pulmonary • Pulmonary embolism Iatrogenic • Right heart catheterization Other • Hyperkalemia • Lenegre’s disease • Lev’s disease ________________________________________________________________________ Left Bundle Branch Block ________________________________________________________________________ DDx of Left Bundle Branch BlockDDx of Left Bundle Branch Block Cardiac • Coronary artery disease • Myocardial infarct • Congestive heart failure • Myocarditis • Cardiomyopathies • Hypertention • Valvular heart disease Other • Endocarditis • Hyperkalemia • Digoxin toxicity 21 Cardiology On ECG
DDx of Long QT segmentDDx of Long QT segment Cardiac • Myocardial infarct Drugs • Antiarrhythmics • Antibiotics o Fluoroquinolones o Erythromycin o Azithromycin o Chloroquine • Antipsychotics o TCA o SSRIs o Haldol o Risperidone • Antihistamines • HIV protease inhibitors • Cocaine • Methadone Metabolic • Hypokalemia • Hypocalcemia • Hypomagnesemia • Hypothyroidism Congenital • Jervell & Lange-Nielsen syndrome • Romano-Ward syndrome • Idiopathic 22 Cardiology On ECG __________________________________________________________________________________________________________________________________________________________________ Prolonged QT Interval ________________________________________________________________________________________________________________________________________________________________ The Short List - Prolonged QT • Myocardial Infarct • Antiarrhtyhmics • Antibiotics • Antipsychotics • Antihistamines • Hypocalcemia
On history: • Dyspnea………………………………….. • Cough……………………………………. • Hemoptysis………………………………. • Pleuritic pain……………………………... On physical: • Clubbing………………………………….. On imaging: • Pleural Effusions…………………………. • Interstitial Infiltrates……………............... • Bilateral Hilar Lymphadenopathy………... • Pulmonary Nodules………………………. • Cavitary Lung Lesions…………………… Chapter 2 Respirology Overview of Topics
DDx of DyspneaDDx of Dyspnea Neuromuscular Neuromuscular disease: • Multiple Sclerosis • Myasthenia Gravis • Guillain Barre syndrome (GBS) • Amyotrophic Lateral Sclerosis (ALS) • Kyphoscoliosis Other: • Stroke • Spinal chord injury • Rib fractures Toxins • Salicylate poisoning • Organophosphate poisoning • Carbon monoxide poisoning Other • Anemia • Metabolic Acidosis • Increased abdominal girth (ie. ascites) • Anaphylaxis • Anxiety/Panic Attack 24 Respirology DDx of DyspneaDDx of Dyspnea Pulmonary Airway Obstruction: • COPD • Asthma • Bronchiectasis • Tumor • Foreign body Parenchymal Disease: • Pneumonia • Pulmonary Edema o Cardiogenic o Non-Cardiogenic (ALI/ARDS) • Intersitial Lung Disease (ILD) Pleural Disease: • Pleural Effusion • Pneumothorax Vascular: • Pulmonary Embolism • Pulmonary Hypertension • Pulmonary Hemorrhage • Vasculitis Cardiac • Coronary artery disease (anginal equivalent) • Congestive Heart Failure • Myocardial Infarction • Pericardial Tamponade The Short List - Acute Dyspnea 1. COPD/Asthma 2. Pneumonia 3. Pulmonary Embolism 4. Pneumothorax 5. CHF ___________________________________________________________________________________________________________________________________________________________________ Dyspnea (Shortness of Breath) ___________________________________________________________________________________________________________________________________________________________________ On history
________________________________________________________________________ Cough ________________________________________________________________________ DDx of CoughDDx of Cough Respiratory Infectious: • Upper respiratory tract infection (URTI) • Pneumonia Non-Infectious: • Postnasal drip • Asthma • Chronic Bronchitis • Bronchiectasis • Lung cancer GI • Gastroesophageal reflux (GERD) Drugs • ACE inhibitors ________________________________________________________________________ Hemoptysis ________________________________________________________________________ DDx of HemoptysisDDx of Hemoptysis Inflammatory • Chronic Bronchitis • Bronchiectasis • Cystic Fibrosis Infectious • Pneumonia • Lung abscess • Tuberculosis • Aspergilloma Neoplastic • Lung Cancer (usually primary) Cardiovascular • Pulmonary Embolism • Congestive Heart Failure • Mitral Stenosis Other • Wegener’s Granulomatosis • Goodpasture’s syndrome • Excessive anticoagulation • Arterio-Venous Malformation (AVM) 25 Respirology The Short List - Hemoptysis 1. Chronic Bronchitis 2. Bronchiectasis 3. Pulmonary Embolism 4. Pneumonia 5. Tuberculosis 6. Lung cancer On history
_______________________________________________________________ Pleuritic Pain _______________________________________________________________ DDx of Pleuritic PainDDx of Pleuritic Pain Pulmonary • Pulmonary Embolism • Pneumothorax • Pneumonia • Viral pleurisy • Pleural effusion Cardiac • Pericarditis _______________________________________________________________ Clubbing _______________________________________________________________ DDx of ClubbingDDx of Clubbing Pulmonary • Lung cancer (primary or metastatic) • Interstitial lung disease (ILD) • Bronchiectasis • Cystic Fibrosis • Lung abscess • Tuberculosis Cardiac • Endocarditis • Atrial myxoma • Congenital heart disease GI • Inflammatory bowel disease (IBD) • Cirrhosis Other • Hyperthyroidism • Thalassemia 26 Respirology Definition • Pleuritic pain (or pleuritic chest pain) is due to inflammation of nerve endings of pain fibers in the pleura. • Pleuritic pain often has a stabbing quality that worsens with inspira- tion, and may be felt most anywhere in the chest. On history/physical
DDx of Exudative Pleural EffusionsDDx of Exudative Pleural Effusions Infectious • Bacterial pneumonia • Tuberculosis • Viral pneumonia • Fungal infection • Parasitic infection Malignancy • Primary Lung Cancer • Metastases • Mesothelioma Respiratory • Pulmonary embolism Inflammatory • Rheumatoid arthritis (large effusion) • SLE (small effusion) • Wegener’s granulomatosis Gastrointestinal • Esophageal rupture • Pancreatitis • Abdominal abscess Other • Hemothorax • Post-CABG • Meigs’s syndrome • Drug induced (ie. amiodarone) DDx of Transudative Pleural EffusionsDDx of Transudative Pleural Effusions Most common • Congestive Heart Failure • Cirrhosis • Nephrotic syndrome • Constrictive Pericarditis Other (usually exudative) • Pulmonary embolism • Malignancy 27 Respirology On physical/imaging ___________________________________________________________________________________________________________________________________________________________________ Pleural Effusion ___________________________________________________________________________________________________________________________________________________________________
DDx of Bilateral Interstitial InfiltratesDDx of Bilateral Interstitial Infiltrates Cardiogenic Pulmonary Edema • Congestive Heart Failure Non-Cardiogenic Pulmonary Edema • ALI • ARDS • Pulmonary embolism • Reperfusion pulmonary edema • Re-expansion pulmonary edema • Neurogenic pulmonary edema o Intracerebral hemorrhage o Subarachnoid hemorrhage o Intracranial surgery o Generalized seizures Diffuse Alveolar Hemorrhage • ARDS • Endocarditis (septic emboli) • Wegener’s granulomatosis • Goodpasture’s syndrome • Pulmonary Infarct • Trauma Infection • Any cause of pneumonia, be it bacterial, viral, or fungal can cause interstitial infiltrates, although special attention should be given to P. jiroveci (PJP, formerly called PCP) Malignancy • Any malignancy (primary or metastatic) • Lymphangitic carcinomatosis 28 Respirology The Short List - Lung Infiltrates 1. CHF 2. ALI/ARDS 3. Hemorrhage 4. Malignancy ___________________________________________________________________________________________________________________________________________________________________ Bilateral Interstitial Infiltrates ___________________________________________________________________________________________________________________________________________________________________ Notes: • Interstitial infiltrates can generally be described as opacification within the lung fields. • This opacification is due to an increase in density of matter at that loca- tion, and can be caused by any of the following: § Water (edema) § Blood (hemorrhage) § Pus (infection) § Tumor On imaging
_______________________________________________________________ Bilateral Hilar Lymphadenopathy _______________________________________________________________ DDx of Bilateral Hilar LymphadenopathyDDx of Bilateral Hilar Lymphadenopathy Rheumatologic • Sarcoidosis Infectious • Tuberculosis • Fungal (ie. Histo, Coccidio) Neoplastic • Lymphoma • Lung cancer • Metastatic disease Other • Pneumoconioses o Silicosis o Berylliosis o Coal-worker’s pneumoconiosis • Prominent pulmonary artery or veins (Pseudo-hilar adenopathy) _______________________________________________________________ Pulmonary Nodules _______________________________________________________________ DDx of Pulmonary NodulesDDx of Pulmonary Nodules Benign • Infectious Granuloma: o Tuberculosis o Histoplasmosis o Coccidioidomycosis o Blastomycosis o Cryptococcus • Other Infections: o Bacterial Abscess o PJP o Aspergilloma • Benign Neoplasms: o Hamartoma o Lipoma o Fibroma • Inflammatory: o Rheumatoid nodule o Wegener’s granulomatosis Malignant • Brochogenic carcinoma • Metastatic 29 Respirology The Short List - Lung Nodules 1. Granuloma (TB) 2. Hamartoma 3. Cancer On imaging
DDx of Cavitary Lung LesionsDDx of Cavitary Lung Lesions Infectious Bacterial: • Bacterial Pneumonia Cavitary lesions caused by bacterial pneumonia are also called pulmonary gangrene. • Endocarditis with septic emboli • Tuberculosis • Abscess Fungal: • Aspergillus • Histoplasma • Coccidoides • Mucor Rheumatologic • Wegener’s Granulomatosis • Rheumatic Arthritis • Sarcoidosis Neoplastic • Primary Lung Cancer • Metastatic Lung Cancer DDx of Cavitary Lung Lesions by SizeDDx of Cavitary Lung Lesions by Size Small Cavitary Lesions Large Cavitary Lesions • Endocarditis with septic emboli • Rheumatoid arthritis • Wegener’s granulomatosis • Lung cancer • Tuberculosis • Abscess • Lung cancer 30 Respirology On imaging ___________________________________________________________________________________________________________________________________________________________________ Cavitary Lung Lesions ___________________________________________________________________________________________________________________________________________________________________ The Short List - Cavitary Lesions 1. Lung cancer 2. Tuberculosis 3. Pneumonia 4. Endocarditis with septic emboli 5. Fungal
General: • Acute Kidney Injury......…………………. • Hematuria………………………………... • Proteinuria.................................................. Acid-Base: • Anion Gap Metabolic Acidosis…..……... • Non-anion Gap Metabolic Acidosis…….. • Metabolic Alkalosis……………...……… Electrolytes: • Hyponatremia……………………………. • Hypernatremia………………………….... • Hypokalemia……………………………... • Hyperkalemia…………………………….. • Hypocalcemia……………………………. • Hypercalcemia………………………...…. • Hypo/Hypermagnesemia………..…...…... • Hypo/Hyperphosphatemia…………...…... Overview of Topics Chapter 3 Nephrology
Pre-RenalPre-Renal Hypovolemia • GI loss • Hemorrhage Decrease in effective circulating fluid volume (ECFV) • Congestive Heart Failure • Sepsis • Shock Renal Artery Pathology • Renal Artery Obstruction: • Stenosis • Thrombosis • Dissection • Abdominal Compartment Syndrome • Renal Artery Vasoconstriction: • NSAIDs • ACE inhibitors • Angiotensin II Receptor Blockers • Hypercalcemia • Other:: • Hepatorenal syndrome Note that abdominal compartment syndrome is usually caused by large-volume ascites compressing blood flow to kidneys, and hence a pre-renal etiology to AKI. Note that abdominal compartment syndrome is usually caused by large-volume ascites compressing blood flow to kidneys, and hence a pre-renal etiology to AKI. 32 Nephrology ____________________________________________________________________________________________________________________________________________ Acute Kidney Injury (Acute Renal Failure) ____________________________________________________________________________________________________________________________________________ Definitions • Acute kidney injury and acute renal failure are synonyms used to describe an acute problem in normal kidney function, although acute kidney injury (AKI) is considered to be the better term. • The approach to acute renal failure is the same as the approach to decreased urine output, or an elevated serum creatinine. They all describe an underly- ing problem with kidney function. • A modern definition of AKI by the Acute Kidney Injury Network (AKIN) defines AKI as an abrupt (within 48 hours) absolute increase in the serum creatinine with one of the following: • A percentage increase in the serum creatinine of ≥ 50% • Serum creatine increase of ≥ 26.4 mmol/L from baseline • Urine output of < 0.5 mL/kg per hour for more than six hours _____________________ Approach: • The approach to AKI involves 3 categories: 1. Pre-Renal 2. Renal 3. Post-Renal
33 Nephrology ____________________________________________________________________________________________________________________________________________ Acute Kidney Injury (continued...) ____________________________________________________________________________________________________________________________________________ The short list - AKI • Pre-Renal • Hypovolemia • CHF • Sepsis/Shock • Renal • ATN • Post-Renal • BPH • Blocked foley RenalRenalRenal Vascular Microangiopathic Hemolytic Anemias (MAHA) • HUS • TTP • DIC Glomerular Glomerulonephritis • Nephrotic • Nephritic Tubulointerstitial Acute Tubular Necrosis (ATN) ______________ Acute Interstitial Nephritis (AIN) Any pre-renal cause Exogenous nephrotoxins • Aminoglycosides • IV Contrast • Chemotherapy Endogenous nephrotoxins • Myoglobin (Rhabdomylosis) • Uric Acid (Tumor Lysis) • Bence Jones protein (Myeloma) ___________________________ Drugs • Antibiotics – Penicillins, Ciprofloxacin • Sulfas – Septra, Lasix, HCTZ • NSAIDs • PPIs • Allopurinol Infiltrative • SLE, Sjogren’s, Sarcoidosis Infectious • Pyelonephritis Post-RenalPost-Renal Anatomic Obstruction • Bilateral Ureteral Obstruction: o Stones o Stricture o Tumor • Bladder Outlet Obstruction o Benign Prostatic Hypertrophy (BPH) o Prostate Cancer o Blocked Foley Catheter o Neurogenic Bladder o Anticholinergic meds
___________________________________________________________________ Acute Kidney Injury (continued...) ___________________________________________________________________ ___________________________________________________________________ Hematuria ___________________________________________________________________ 34 Nephrology AKI Lab Workup • Urinanalysis (U/A) • Fractional excretion of sodium (FE Na) • Urine eosinophils (if warranted) • Renal ultrasound (if warranted, to rule out obstruction) • Renal biopsy (if suspecting GN) Urinalysis findings Pre-renal • Often bland, can have Hyaline casts • FENA <1% • Note that CKD patients with pre-renal AKI can have an FENA >1% due to their decreased capacity for tubular sodium reabsorption Renal GN: • RBC casts • Dysmorphic RBCs ATN: • Granular casts (muddy brown casts) • Mild proteinuria and/or hematuria (RBCs) • FENA >2% AIN • Positive eosinophils • WBC casts (if pyelonephritis) Post-renal • Often bland • Can have hematuria DDx of HematuriaDDx of Hematuria Extra-renal (more common) Infection: • Cystitis • Urethritis • Prostatitis Neoplasm: • Prostate cancer • Bladder cancer (transitional cell cancer) Other: • Foley trauma • Nephrolithiasis Intra-renal • Nephrolithiasis • Renal cell carcinoma • Renal infarcts • Renal vein thrombosis • Trauma • Glomerulonephritis • Polycystic kidney disease Note that common systemic causes of GN that can cause hematuria to be kept in mind at the very least are SLE, Vasculitis, Endocarditis, HIV/Hep B/Hep C. Note that common systemic causes of GN that can cause hematuria to be kept in mind at the very least are SLE, Vasculitis, Endocarditis, HIV/Hep B/Hep C.
DDx of ProteinuriaDDx of Proteinuria Glomerular • Glomerulonephritis Tubulointerstitial • ATN • AIN Hemodynamic • Hypertension (Hypertensive nephrosclerosis) • Hypertensive emergency • Congestive heart failure Overproduction of LMW proteins • Multiple Myeloma • Waldenstrom's Macroglobulinemia Hereditary • Alport's syndrome • Fabry's disease • Polycystic Kidney disease Other • Heavy Exercise • Fever • Infection • Orthostatic proteinuria Note that common systemic causes of GN that can cause proteinuria to be kept in mind are Diabetes, SLE, Amyloid/Multiple Myeloma. Note that common systemic causes of GN that can cause proteinuria to be kept in mind are Diabetes, SLE, Amyloid/Multiple Myeloma. 35 Nephrology Proteinuria Lab Workup • Urine dipstick: o Fast & cheap, but inaccurate in terms of quantification o Dipstick only becomes positive after 300 mg of protein is present within the urine, therefore it will not detect microalbuminemia o Dipstick only detects negatively charged proteins (ie. albumin), hence will not detect paraproteins involved in plasma cell dyscra- sias such as multiple myeloma necessarily. • Urine Albumin to Creatinine Ratio (ACR) versus 24 hour urine protein col- lection. Urine ACR is obviously easier for patients since it does not in- volve 24 hour urine collection. Diagnostic Hints: Diagnostic Approach to ProteinuriaDiagnostic Approach to Proteinuria If proteinuria < 1.5g per day, then likely etiologies are: Functional • Fever • Infection • Exercise • Orthostatic Overflow • Multiple Myeloma • Waldenstrom’s If proteinuria >1.5g per day, then likely etiologies are: • Glomerulonephritis • ATN • AIN ____________________________________________________________________________________________________________________________________________ Proteinuria ____________________________________________________________________________________________________________________________________________
DDx of Anion Gap Metabolic AcidosisDDx of Anion Gap Metabolic Acidosis Ketoacidosis • Diabetic ketoacidosis (DKA) • Alcoholism • Starvation Lactic Acidosis • Type A = impairment in tissue oxygenation o Shock (4 subtypes) o Respiratory distress o Sepsis o Ischemic Bowel • Type B = no impairment in tissue oxygenation o Meds: Metformin, ASA, NRTI o Alcoholism o Malignancy Renal Failure • Any cause of Renal Failure (Acute and/or Chronic) Drugs • Salicylates • Acetaminophen • Methanol • Ethylene Glycol • Paraldehyde • Cyanide 36 Nephrology Approach to Metabolic Acidosis Definition: • Acidosis = pH <7.4 (some sources indicate pH<7.35) • Metabolic acidosis = Gain of Hydrogen or loss of Bicarbonate Diagnosis: Step 1: • Look at electrolyte panel for a low bicarbonate. • If bicarbonate low, suspect metabolic acidosis Step 2: • Perform an arterial blood gas (ABG) to look for acidosis (pH <7.4) • If acidosis is present, with a low bicarbonate, it will confirm pres- ence of underlying metabolic acidosis Step 3: • Calculate the Anion Gap (AG) = Na+ - (Cl- + HCO3-) • An elevated AG is defined as >12 (if albumin normal) • For every 10 unit decrease in albumin, add 3 units to the AG to get an AG corrected for low albumin Step 4: • Calculate compensation – 1:1 bicarbonate to CO2 • In other words, for every decrease in 1 unit for bicarbonate, the CO2 also should decrease by 1 to compensate ____________________________________________________________________________________________________________________________________________ Anion Gap Metabolic Acidosis (AGMA) ____________________________________________________________________________________________________________________________________________
37 Nephrology Approach to Metabolic Acidosis (continued) Step 5: • Measure the delta-delta Delta-Delta Delta-Delta = delta AG/ delta HCO3- = (expected AG - calculated AG)/ (24 – HCO3-) = (12 - calculated AG) / (24 – HCO3-) • The delta-delta is only useful in Anion Gap Metabolic Acidosis to see if there are multiple acid-base disturbances present on top of An- ion Gap Metabolic Acidosis • This is particularly useful if the compensation does not add up 1:1 Delta-Delta Significance 1-2 <1 >2 AG met acidosis AG met acidosis + non-AG met acidosis AG met acidosis + met alkalosis AGMA Lab Workup: • Creatinine & BUN • Lactate • Ketones: o Plasma beta-hydroxybutyrate o Urine dipstick acetoacetate • Serum Toxin Screen: o Salicylates o Acetaminophen o Ethanol • Serum osmolality: o Calculate osmolal gap if suspecting an underlying toxic ingestion o An elevated osmolal gap suggests the presence of an unmeasured osmole o Causes of an elevated osmolal gap (>10) are: DDx for Elevated Osmolal Gap • Methanol • Ethylene glycol • Ethanol • Isopropyl alcohol Ethanol and isopropyl alcohol do not cause an AGMA ____________________________________________________________________________________________________________________________________________ Anion Gap Metabolic Acidosis (continued...) ____________________________________________________________________________________________________________________________________________
38 Nephrology Osmolal Gap (OG) • OG = measured serum osmolality − calculated osmolality • Calculated osmolality = 2 x [Na mmol/L] + [glucose mmol/L] + [urea mmol/L] • It the difference between the two osmlalities is >10 (or >12 according to some sources), then it suggests that there is an underlying toxic ingestion • As the toxin is metabolized, the osmolal gap corrects back to normal quicker than the anion gap, so you may have a high AG but normal OG. Don’t be fooled. • Note: a mnemonic to remember the calculated osmolality formula of 2Na + glucose + BUN is “2 salty, sticky, buns” ____________________________________________________________________________________________________________________________________________ Anion Gap Metabolic Acidosis (continued...) ____________________________________________________________________________________________________________________________________________
DDx of Non-Anion Gap Metabolic AcidosisDDx of Non-Anion Gap Metabolic Acidosis Positive Urine Anion Gap • Early Renal Failure • RTA type I • RTA type IV Negative Urine Anion Gap • RTA type II • Diarrhea (GI loss of HCO3-) • Rapid infusion of bicarbonate-free IV fluids (dilutional) • Drugs: o Sevelamer o Cholestyramine o Acetazolamide o Toluene 39 Nephrology Urine Anion Gap (UAG) Calculation Urine Anion Gap = (Urine Na + Urine K) – Urine Cl Note: UAG interpretation assumes that the patient is not hypovolemic and has no AG metabolic acidosis. Renal Tubular Acidosis (RTA) Details: RTA Type I RTA Type II RTA Type IV Site Distal Proximal Distal Primary defect Defective distal H+ secretion Decreased proximal reabsorption of HCO3- Hypoaldosteronism Plasma bicarbonate Variable, may be below 10 meq/L 12 to 20 meq/L > 17 meq/L Plasma Potassium Hypokalemia largely corrects with alkali therapy Hypokalemia made worse by bicarbonaturia induced by alkali therapy Hyperkalemia ____________________________________________________________________________________________________________________________________________ Non-Anion Gap Metabolic Acidosis (NAGMA) ____________________________________________________________________________________________________________________________________________
___________________________________________________________________ Metabolic Alkalosis ___________________________________________________________________ DDx of Metabolic AlkalosisDDx of Metabolic Alkalosis Gastrointestinal H+ loss • Vomiting • NG suction • Antacids in Chronic Kidney Disease Renal H+ loss • Diuretics (loop or thiazide) • Hypercalcemia • Hyperaldosteronism • Post-hypercapnic alkalosis Intracellular H+ shift • Hypokalemia Contraction alkalosis Any cause of hypovolemia, particularly: • GI loss • Diuresis ______________________________________________________________________________ Hyponatremia _____________________________________________________________________________ 40 Nephrology Overview: • Hyponatremia is not a deficit in sodium, but in fact relates to serum tonicity and volume status. • There are 2 parts to the differential diagnosis of hyponatremia: firstly one is based on the serum tonicity, and then the second part is a specific differen- tial diagnosis for hypotonic hyponatremia, which is the most common etiol- ogy for hyponatremia. DDx of HyponatremiaDDx of Hyponatremia Hypotonic Hypotonic hyponatremia is the most common cause of hyponatremia. See next page for the differential diagnosis of hypotonic hyponatremia. Isotonic Lab artifact from: • Hyperlipidemia • Hyperproteinemia Hypertonic Excess of an osmole that draws water intravascularly, particularly: • Hyperglycemia • Mannitol Note that every increase in glucose by 10 mmol/L causes a decrease in sodium by 3 mEq/L Note that every increase in glucose by 10 mmol/L causes a decrease in sodium by 3 mEq/L
41 Nephrology DDx of Hypotonic HyponatremiaDDx of Hypotonic Hyponatremia Hypervolemic • Congestive heart failure • Cirrhosis • Nephrotic syndrome • Advanced renal failure DDx of Hypotonic HyponatremiaDDx of Hypotonic Hyponatremia Hypovolemic Renal losses: • Diuretics • Hypoaldosteronism Extrarenal losses: • Vomiting • Diarrhea • Pancreatitis • Inadequate intake Euvolemic SIADH: • Any intracranial/CNS disorder • Any pulmonary disease • Drugs o Antidepressants o Antipsychotics o Carbamazepine • Miscellaneous o Pain o Nausea o Postoperative state Endocrine disorders o Hypothyroidism o Adrenal insufficiency Suppressed ADH: • Low solute diet/malnutrition • Psychogenic polydipsia • Pregnancy ____________________________________________________________________________________________________________________________________________ Hyponatremia (continued...) ____________________________________________________________________________________________________________________________________________ The Short List - Hyponatremia 1. Hypovolemia 2. SIADH 3. Hypothyroidism 4. Adrenal insufficiency 5. Low solute diet 6. Hypervolemia
42 Nephrology Approach Step 1: Determine if the patient is symptomatic: • Severe Symptoms: seizure, lethargy, stupor, coma. If so, this is a medical emergency should be treated immediately (see manage- ment) • Absence of Severe Symptoms: continue to Step 2 Step 2: Determine the serum osmolality: • HyperOSM (>300 mOsm/kg): Hyperglycemia (ie. DKA or HHS) - correct by adding 3mmol/L of Na for every 10mmol/L ↑ in glucose • IsoOSM (275-300 mOsm/kg): severe paraproteinemia (myeloma) or hypertriglyceridemia • HypoOSM (<275 mOsm/kg): continue to Step 3 Step 3: Determine the urine osmolality: • Low (<100 mOSM/kg): due to psychogenic polydipsia or de- creased solute intake (beer potomania, tea and toasters) • Non-Low (>100 mOSM/kg): Continue to step 4 Approach (...) Step 4. Determine the patient’s volume status: • Hypervolemic - CHF, Cirrhosis, Nephrotic syndrome • Hypovolemic - renal vs extrarenal losses of fluid • Euvolemic – SIADH vs other Step 5. Treat the underlying cause SIADH Findings • Euvolemic • Urine osmolality at least >100, usually >300 • Urine sodium >40 ____________________________________________________________________________________________________________________________________________ Hyponatremia (continued...) ____________________________________________________________________________________________________________________________________________
___________________________________________________________________ Hypernatremia ___________________________________________________________________ DDx of HypernatremiaDDx of Hypernatremia Extra-renal Water Loss • Vomiting • NGT • Diarrhea • Insensible losses (fever, exercise) Renal Water Loss • Diuretics • Diabetes insidipus: Central: o Tumor o Trauma o Infiltrative disease o Hypoxic encephalopathy Nephrogenic: o Lithium o Hypercalcemia o Recovery phase of ATN o Post-obstruction Other • Hypertonic saline administration • Hyperaldosteronism • Seizures ___________________________________________________________________ Hypokalemia ___________________________________________________________________ DDx of HypokalemiaDDx of Hypokalemia Increased entry into cells • Insulin • Beta agonists • Alkalosis • Hypothermia Increased GI loss • Diarrhea Note: Vomiting and NG tube drainage cause hypokalemia but manifest as renal losses due to metabolic alkalosis and secondary hyperaldosteronism Increased Renal loss • Diuretics • Hypomagnesemia • Renal Tubular Acidosis (RTA) types I and II • Hyperaldosteronism • Bartter’s & Gitelman’s syndromes Other • Dialysis • Plasmapheresis 43 Nephrology Note: Hypernatremia is a deficit of water relative to sodium. It is usually from a loss of hypotonic fluid and impaired access to free water. Therefore, all pa- tients with hypernatremia are hypertonic. Hypokalemia On ECGHypokalemia On ECG Hypokalemia - Prolonged, flat T waves - U waves - ST depression
DDx of Hypokalemia associated with Acid-Base Abnormalities: Hypokalemia and Acid-Base AbnormalitiesHypokalemia and Acid-Base Abnormalities Hypokalemia and metabolic acidosis (NAGMA) • RTA type I • RTA type II Hypokalemia and metabolic alkalosis Low urine chloride (<20): • Vomiting • NG tube drainage • Diuretics High urine chloride (>40): • Hyperaldosteronism • Bartter’s & Gitelman’s syndromes 44 Nephrology Notes on Hypokalemia • Oral replacement with Potassium Chloride (KCl) is preferable over intra- venous KCL since potassium can be more rapidly repleted orally. • Oral KCl can be given either in solid (K-Dur) or liquid format (K- Elixir). The K-Dur is a large pill that is sometimes difficult to swallow for patients, while the K-Elixir tastes awful according to many patients. There is otherwise no noted difference in effectiveness between the two. • Patients with hypomagnesemia often need magnesium supplementation in addition to potassium supplementation in order to correct their hypo- kalemia. ____________________________________________________________________________________________________________________________________________ Hypokalemia (continued...) ____________________________________________________________________________________________________________________________________________
DDx of HyperkalemiaDDx of Hyperkalemia Increased release from cells Cell lysis • Hemolysis • Rhabdomyolysis • Tumor lysis syndrome Cell release: • Digoxin overdose • Beta blockers • Metabolic acidosis • Hyperglycemia/Insulin deficiency (ie. DKA) Decreased urinary excretion • Renal failure (Acute or Chronic) • Hypoaldosteronism/RTA type 4 45 Nephrology Hyperkalemia on ECG On ECGOn ECG Hyperkalemia In chronological order based on severity: 1. Tall, Peaked T waves (usually 1st change seen) 2. Increased PR interval 3. Wide QRS 4. Loss of P wave 5. Sine wave (severe, late change) ____________________________________________________________________________________________________________________________________________ Hyperkalemia ____________________________________________________________________________________________________________________________________________
DDx of HypocalcemiaDDx of Hypocalcemia Pseudo- hypoparathyroidism (high PTH) • PTH end organ resistance Hypoparathyroidism (low PTH) • Hypomagnesemia • Thyroidectomy • Parathyroidectomy • Radiation induced destruction of parathyroids • Infiltration of parathyroid (ie. hemochromatosis) Vit D deficiency • Low sunlight exposure • Gut Malabsorption (IBD, Celiac, etc) • Drugs (anticonvulsants, ketoconazole) CKD • CKD (secondary hyperparathyroidism) Calcium sequestration • Pancreatitis • Hyperphosphatemia (AKI, Rhabdo, Tumor lysis) • Blood transfusions (citrate binding to calcium) 46 Nephrology Hypocalcemia on ECG On ECGOn ECG Hypocalcemia Prolonged QT segment Hypocalcemia Treatment • Calcium supplementation o IV Calcium gluconate or Calcium chloride in severe hypocalcemia or in symptomatic patients o PO Calicum carbonate in asymptomatic patients • Magnesium sulfate (MgSO4) o If Magnesium levels are low, do not forget to replete as well to en- sure that Calcium is well absorbed o Usually recommended to repeat dosing 2 to 3 times, several hours apart, to ensure correction since magnesium sulfate is not readily absorbed • Vitamin D (Ergocalciferol or Cholecalciferol) o Administer in vitamin D deficiency ____________________________________________________________________________________________________________________________________________ Hypocalcemia ____________________________________________________________________________________________________________________________________________
47 Nephrology Hints & Tips • Before establishing a diagnosis of hypercalcemia, serum calcium needs to be corrected for albumin level. This means, for every 10 unit decrease in the albumin, you must add 0.2 units to the serum calcium to have a cor- rected level • Alternatively you can order a serum ionized calcium level, which will give you the actual serum calcium regardless of albumin levels • Primary hyperparathyroidism and malignancy account for the majority of cases of hypercalcemia • The presence of longstanding asymptomatic hypercalcemia is more sug- gestive of primary hyperparathyroidism • Primary hyperparathyroidism is often associated with mild hypercalce- mia, with serum levels often <2.75 mmol/L. Serum calcium values >3.25 mmol/L are unusual in primary hyperparathyroidism and are more com- mon in malignancy On ECG: On ECGOn ECG Hypercalcemia • Shortened QT segment ____________________________________________________________________________________________________________________________________________ Hypercalcemia ____________________________________________________________________________________________________________________________________________ DDx of HypercalcemiaDDx of Hypercalcemia PTH-mediated (High PTH) • Primary Hyperparathyroidism • Tertiary hyperparathyroidism (chronic kidney disease) • Familial hypocalciuric hypercalcemia (FHH) • Lithium PTH-independent (low PTH) Malignancy: • Leukemia, Lymphoma, Multiple Myeloma • Humoral (PTH-related protein): o Squamous cell carcinomas (lung/esophagus) o Breast/Renal/Bladder/Ovarian carcinoma • Bone metastases: o Breast/Lung/Thyroid/Kidney/Prostate cancers Endocrine: • Hyperthyroidism • Adrenal insufficiency Drugs: • Thiazides (ie. HCTZ) • Vitamin D intoxication • Vitamin A intoxication • Excessive Calcium Carbonate Granulomatous disorders (cause 1-25-Vit D excess): • Tuberculosis • Sarcoidosis • Wegener’s granulomatosis Other: • Immobilization
48 Nephrology Hypercalcemia - Workup • The first step in the investigation of hypercalcemia is to get a PTH level, in addition to Calcium and Phosphate levels. • An elevated PTH value or a PTH value in the upper half of the normal range in the setting of hypercalcemia is likely the result of primary hy- perparathyroidism. • PTH concentrations that are normal or low indicate the need for evalua- tion of causes other than primary hyperparathyroidism as the etiology for the hypercalcemia. Theses tests include: o 24 hour urinary calcium excretion o Urine calcium to creatinine clearance ratio (Ca/Cr clearance) (also known as urine fractional excretion of calcium (FE Ca)) o PTH related peptide (PTHrp) o SPEP & UPEP o TSH o 1,25-dihydroxyvitamin D (calcitriol) o 25-hydroxyvitamin D (calcidiol) o Vitamin A • The urine calcium to creatinine clearance ratio is measured from a fast- ing morning spot urine collection. The formula for determining the cal- cium to creatinine clearance ratio is (urine calcium × serum creatinine)/ (serum calcium × urine creatinine) • Note that elevated levels of calcitriol are suggestive of underlying lym- phoma or granulomatous disorders, whil elevated calcidiol levels are indicative of vitamin D intoxication ____________________________________________________________________________________________________________________________________________ Hypercalcemia (continued) ____________________________________________________________________________________________________________________________________________
___________________________________________________________________ Hypomagnesemia ___________________________________________________________________ DDx of HypomagnesemiaDDx of Hypomagnesemia GI loss • Vomiting • Diarrhea • NG suction • Pancreatitis (saponification of Mg in necrotic fat) Renal loss Drugs: • Diuretics (loops and thiazides) • Alcohol • Aminoglycosides Other: • Hypercalcemia (Ca & Mg compete for transport in the Loop of Henle) • Hyperaldosteronism • Primary renal wasting (hereditary, diagnosis of exclusion) ___________________________________________________________________ Hypermagnesemia ___________________________________________________________________ DDx of HypermagnesemiaDDx of Hypermagnesemia Decreased loss • Renal failure Increased intake • Oral ingestion • IV infusion Other • Diabetic ketoacidosis • Tumor lysis syndrome • Adrenal insufficiency • Lithium 49 Nephrology
___________________________________________________________________ Hypophosphatemia ___________________________________________________________________ DDx of HypophosphatemiaDDx of Hypophosphatemia Redistribution (Intracellular shift) • Insulin • Acute respiratory alkalosis • Hungry bone syndrome Decreased intestinal absorption • Inadequate intake • Chronic diarrhea • Vitamin D deficiency • Antacids Increased urinary excretion • Hyperparathyroidism • Acute volume expansion • Osmotic diuresis 
 ___________________________________________________________________ Hyperphosphatemia ___________________________________________________________________ DDx of HyperphosphatemiaDDx of Hyperphosphatemia Intracellular release • Tumor lysis syndrome • Rhabdomyolysis • Lactic acidosis • Ketoacidosis Increased renal reabsorption • Hypoparathyroidism • Acromegaly • Bisphosphonates Decreased renal loss • Renal failure Pseudohyperphosphatemia • Hyperglobulinemia (Multiple myeloma) • Hyperlipidemia • Hyperbilirubinemia 50 Nephrology
On history: • Oropharyngeal Dysphagia……………… • Esophageal Dysphagia…………….... • Abdominal Pain………………………......... • Upper GI Bleed…………………………...... • Lower GI Bleed…………………………..... • Diarrhea…………………………………........ • Bloody Diarrhea…………………………... • Constipation……………………………….... On physical: • Hepatomegaly………………………….….   • Splenomegaly……………………............. • Ascites…………………………………........ On labs: • Elevated Transaminases……………………... • Elevated Biliary Tract Enzymes …………..   • Conjugated Hyperbilirubinemia………….… • Unconjugated Hyperbilinemia……………... • Hypoalbuminemia…………………………....... • Elevated amylase…………………….…. • Elevated lipase…………………….……. Chapter 4 Gastro- enterology Overview of Topics
___________________________________________________________________ Oropharyngeal Dysphagia ___________________________________________________________________ DDx of Oropharyngeal DysphagiaDDx of Oropharyngeal Dysphagia Neurological • Stroke • Parkinson’s disease • Bell’s palsy Neuromuscular • Myasthenia gravis • Multiple sclerosis • Amyotrophic lateral sclerosis (ALS) • Polymositis • Muscular dystrophy Other • Zencker’s Diverticulum • Pharyngitis • Enlarged thyroid • Neck mass ___________________________________________________________________ Esophageal Dysphagia ___________________________________________________________________ DDx of DysphagiaDDx of Dysphagia Solids Only (Mechanical Obstruction) • Intermittent: o Esophageal rings (in lower esophagus) o Esophageal webs (in upper esophagus) • Progressive: o Peptic stricture o Esophageal cancer Solids and/or Liquids (Motility Disorder) • Intermittent: o Diffuse esophageal spasm (DES) o Non-specific esophageal motility disorder (NEMD – dx of exclusion) • Progressive: o Achalasia o Scleroderma 52 Gastroenterology Notes • Oropharyngeal dysphagia is defined as a difficulty in initiating swallow- ing. It can be often associated with coughing, choking, and/or nasal re- gurgitation of food. • Oropharyngeal dysphagia is caused by underlying neurologic or muscu- lar disease. Notes • Esophageal dysphagia is defined as a sensation of food getting stuck or lodged in the esophagus. • Esophageal dysphagia of solids only is due to an underlying mechanical obstruction, whereas in esophageal dysphagia with both solids and liq- uids, there is an underlying motility disorder. • Note that achalasia is the most common etiology among the motility disor- ders causing esophageal dysphagia On history
DDx of Abdominal PainDDx of Abdominal Pain Epigastric • Pancreatitis • GERD • Peptic Ulcer Disease • Gastritis • Gastroenteritis • Myocardial Infarct • Ruptured Aortic Aneurysm Periumbilical • Early Appendicitis • Ruptured Aortic Aneurysm • Gastroenteritis • Bowel obstruction Diffuse Abdominal: • Gastroenteritis • Bowel ischemia • Peritonitis • Irritable Bowel Syndrome Other: • Diabetic ketoacidosis • Porphyria • Malaria • Familial Mediterranean fever 53 Gastroenterology DDx of Abdominal PainDDx of Abdominal Pain Right Upper Quadrant • Hepatitis • Cholecystitis • Cholangitis • Budd-Chiari syndrome • Pneumonia/Empyema/Pleurisy • Sub-diaphragmatic abscess Left Upper Quadrant • Gastritis • Gastric Ulcer • Splenic Infarct • Splenic Abscess Right Lower Quadrant • Appendicitis • Inflammatory Bowel Disease • Nephrolithiasis • Inguinal Hernia • Pelvic Inflammatory Disease • Ectopic pregnancy Left Lower Quadrant • Diverticulitis • Inflammatory Bowel Disease • Nephrolithiasis • Inguinal Hernia • Pelvic Inflammatory Disease • Ectopic pregnancy ____________________________________________________________________________________________________________________________________________ Abdominal Pain ____________________________________________________________________________________________________________________________________________ On history
___________________________________________________________________ Upper GI Bleed (UGIB) ___________________________________________________________________ DDx of UGIBDDx of UGIB Ulcerative/Erosive • Peptic Ulcer Disease • Esophagitis Portal Hypertension • Esophageal Varices • Gastric Varices • Duodenal Varices Traumatic • Mallory-Weiss tear Neoplastic • Benign tumor • Adenocarcinoma • Kaposi’s sarcoma Vascular • Angiodysplasia • Osler-Weber-Rendu syndrome ___________________________________________________________________ Lower GI Bleed (LGIB) ___________________________________________________________________ DDx of LGIBDDx of LGIB Anatomical • Diverticulosis Vascular • Angiodysplasia • Ischemic colitis/Mesenteric ischemia • Radiation-induced telangiectasia Inflammatory • Infectious colitis • Inflammatory Bowel Disease Neoplastic • Polyp • Carcinoma Other • Hemorrhoid • Anal Fissure • Ulcer 54 Gastroenterology On history
DDx of Bloody DiarrheaDDx of Bloody Diarrhea Infectious Bacterial: • E. coli (2 types): o Entero-invasive o 0157:H7 • Salmonella • Shigella • Campylobacter • Yersinia enterocolitica • Vibrio (less likely) • C. difficile (if toxic megacolon) Viral: • CMV colitis (in immunosuppressed) Parasitic: • Entamoeba histolytica Inflammatory • Inflammatory bowel disease (IBD) • Bowel ischemia • Diverticulosis • Radiation enteritis Neoplastic • Colon cancer • Lymphoma 55 Gastroenterology On history ____________________________________________________________________________________________________________________________________________ Bloody Diarrhea ____________________________________________________________________________________________________________________________________________ The Short List - Bloody Diarrhea 1. Bacterial 2. Viral 3. Parasitic 4. IBD 5. Diverticulosis 6. Colon cancer
DDx of Non-Bloody DiarrheaDDx of Non-Bloody Diarrhea Infectious Bacteria: • C. difficile • Staph aureus • Clostridium perfringens • Bacillus cereus • Vibrio cholera & parahaemolyticus • Mycobacterium avium (in immunosuppressed) Viruses: • Rotavirus • Norovirus • Adenovirus • CMV (in immunosuppressed) Other: • Giardia • Note: all infectious causes of bloody diarrhea can also potentially present as non-bloody diarrhea • Note: all infectious causes of bloody diarrhea can also potentially present as non-bloody diarrhea Inflammatory • Inflammatory bowel disease (Crohn’s > UC) • Bowel ischemia • Diverticulitis • Radiation enteritis Neoplastic • Colon cancer • Lymphoma within the GI tract DDx of Non-Bloody DiarrheaDDx of Non-Bloody DiarrheaDDx of Non-Bloody Diarrhea Malabsorption Bile salt deficiency: • Cirrhosis Pancreatic insufficiency: • Chronic pancreatitis Mucosal abnormalities: • Bacterial overgrowth • Lactose intolerance • Celiac disease • Tropical sprue • Whipple’s disease Bile salt deficiency: • Cirrhosis Pancreatic insufficiency: • Chronic pancreatitis Mucosal abnormalities: • Bacterial overgrowth • Lactose intolerance • Celiac disease • Tropical sprue • Whipple’s disease Secretory • Gastrinoma (Zollinger-Ellison syndrome) • VIPoma • Carcinoid tumor • Laxative abuse • Gastrinoma (Zollinger-Ellison syndrome) • VIPoma • Carcinoid tumor • Laxative abuse Motility • Irritable bowel syndrome • Scleroderma • Diabetic autonomic neuropathy (or dysmotility) • Irritable bowel syndrome • Scleroderma • Diabetic autonomic neuropathy (or dysmotility) • Hyperthyroidism, although commonly included in the ddx for diarrhea, in fact does not truly present with diarrhea but instead with an increased incidence of bowel movements • Hyperthyroidism, although commonly included in the ddx for diarrhea, in fact does not truly present with diarrhea but instead with an increased incidence of bowel movements • Hyperthyroidism, although commonly included in the ddx for diarrhea, in fact does not truly present with diarrhea but instead with an increased incidence of bowel movements 56 Gastroenterology On history ____________________________________________________________________________________________________________________________________________ Non-Bloody Diarrhea ____________________________________________________________________________________________________________________________________________
___________________________________________________________________ Chronic Diarrhea ___________________________________________________________________ DDx of Chronic DiarrheaDDx of Chronic Diarrhea Infectious • HIV and related infections Inflammatory • Inflammatory bowel disease • Microscopic colitis • Radiation enteritis Malabsorption Bile salt deficiency: • Cirrhosis Pancreatic insufficiency: • Chronic pancreatitis Mucosal abnormalities: • Bacterial overgrowth • Lactose intolerance • Celiac disease, Tropical sprue, Whipple’s disease Secretory • Gastrinoma (Zollinger-Ellison syndrome) • VIPoma • Carcinoid tumor • Laxative abuse • Short bowel syndrome • Post-cholecystectomy • Bile acids are re-absorbed in the terminal ileum. In patients with no terminal ileum (ie. short bowel syndrome), excessive amounts of bile acids enter the colon and cause diarrhea. Similar principle applies post- cholecystectomy. • Bile acids are re-absorbed in the terminal ileum. In patients with no terminal ileum (ie. short bowel syndrome), excessive amounts of bile acids enter the colon and cause diarrhea. Similar principle applies post- cholecystectomy. ___________________________________________________________________ Constipation ___________________________________________________________________ DDx of ConstipationDDx of Constipation Obstruction • Cancer • Stricture Endocrine • Diabetes mellitus • Hypothyroidism • Panhypopituitarism • Pregnancy Metabolic • Hypokalemia • Hypercalcemia Drugs • Opiates • Antidepressants • Antipsychotics • Antihistamines • Iron supplements Neurogenic • Parkinson’s disease • Multiple sclerosis • Spinal cord injury 57 Gastroenterology On history
DDx of HepatomegalyDDx of Hepatomegaly Cirrhotic • Any cause of cirrhosis Neoplastic • Hepatocellular carcinoma • Leukemia • Lymphoma • Multiple Myeloma Infectious • Infectious Mononucleosis • Hepatitis • Liver abscess • Malaria Metabolic • Amyloidosis • Fatty liver disease (steatohepatitis) Drugs • Alcohol Cardiac • Right heart failure 58 Gastroenterology On physical The Short List - Hepatomegaly 1. Cirrhosis 2. Leukemia/Lymphoma 3. Infectious Mononucleosis 4. Fatty liver disease 5. Right heart failure ____________________________________________________________________________________________________________________________________________ Hepatomegaly ____________________________________________________________________________________________________________________________________________
DDx of SplenomegalyDDx of Splenomegaly Hematologic/ Neoplastic • Leukemia • Lymphoma • Multiple myeloma • Myelofibrosis • Polycythemia vera • Essential thrombocytosis • Sickle cell disease • Metastatic solid tumors Infectious Viral: • EBV (infectious mononucleosis) • CMV • HIV Bacterial: • Endocarditis • Tuberculosis Parasitic: • Malaria • Schistosomiasis Congestive • Right Heart failure • Cirrhosis • Thrombosis of portal, hepatic, or splenic veins Inflammatory • Sarcoidosis • Systemic lupus erythematosus (SLE) • Rheumatoid arthritis 59 Gastroenterology The Short List - Splenomegaly 1. Leukemia 2. Lymphoma 3. Metastatic solid tumor 4. Infectious Mononucleosis 5. CHF 6. Cirrhosis On physical ____________________________________________________________________________________________________________________________________________ Splenomegaly ____________________________________________________________________________________________________________________________________________
DDx of AscitesDDx of Ascites SAAG > 11 (Portal Hypertension related) Pre-Sinusoidal: • Portal vein thrombosis • Splenic vein thrombosis • Schistosomiasis Sinusoidal: • Cirrhosis • Spontaneous Bacterial Peritonitis • Acute Hepatitis • Malignancy • Hepatocellular carcinoma • Pancreatic adenocarcinoma • Metastatic disease to liver/pancreas Post-Sinusoidal: • Right sided CHF • Budd-Chiari syndrome SAAG <11 (No Portal Hypertension) Infectious: • Peritonitis • Tuberculosis • HIV • Pelvic Inflammatory Disease Other: • Peritoneal carcinomatosis • Pancreatitis • Hypoalbuminemia • Dialysis • Meig’s syndrome 60 Gastroenterology The Short List - Ascites 1. Cirrhosis 2. CHF 3. Malignancy Approach • The differential of ascites is often first based upon the Serum Album to Ascites Gradient (SAAG). SAAG = Serum Albumin – Ascites Albumin • A SAAG of greater than 11 is related to underlying portal hypertension. Think of this as being similar in underlying physiology to a transudative effusion. • A SAAG of less than 11 is not related to any underlying portal hyperten- sion. Think of this as being similar to an exudative effusion. • It is important to note malignancies that cause cirrhosis and resultant por- tal hypertension present with a SAAG >11. Malignancies such as perito- neal carcinomatosis which do not cause cirrhosis, will present with a SAAG <11. On physical/ On labs ____________________________________________________________________________________________________________________________________________ Ascites ____________________________________________________________________________________________________________________________________________
DDx of TransaminitisDDx of Transaminitis Infectious • Hepatitis A, B, C, D, & E • HIV/CMV/EBV/HSV Drugs Most common: • Alcohol • Acetaminophen Other: • Statins • Amiodarone • Azoles (Fluconazale/Itraconazole/Voriconazole) • Antiepileptics - Phenytoin • Anti-Tuberculosis drugs - INH, Rifampin • Propylthiouracil (PTU) • Chemotherapy Metabolic • Non-alcoholic steatohepatitis (NASH) • Non-alcoholic fatty liver disease (NAFLD) Vascular • Congestive heart failure • Ischemic hepatitis (“shock liver”) • Budd-Chiari syndrome Hereditary • Hemochromatosis • Wilson’s disease • Alpha-1-antitrypsin deficiency • Celiac disease Autoimmune • Autoimmune hepatitis 61 Gastroenterology On labs ____________________________________________________________________________________________________________________________________________ Elevated Transaminases (Transaminitis/Elevated AST&ALT) ____________________________________________________________________________________________________________________________________________ Transaminitis in Pregnancy: In patients who develop transaminitis during pregnancy, the usual causes should be ruled out, in addition to looking for pregnancy specific causes, outlined below: DDx of Pregnancy-induced TransaminitsDDx of Pregnancy-induced Transaminits 1st trimester • Nausea & vomiting of pregnancy (NVP) 2nd & 3rd trimesters • Acute fatty liver of pregnancy • Cholestasis of pregnancy • Pre-eclampsia/Eclampsia • HELLP syndrome The Short List - Transaminitis 1. Infectious - Hepatitis B & C 2. Drugs - Alcohol & Tylenol 3. Vascular - CHF & Shock 4. Hereditary - Hemochromatosis 5. NAFLD
___________________________________________________________________ Elevated Biliary Tract Enzymes (ALK & GGT) ___________________________________________________________________ DDx of elevated ALK & GGTDDx of elevated ALK & GGT Biliary obstruction • Cholecystitis • Choledocholithiasis • Ascending cholangitis • Primary sclerosing cholangitis • Primary biliary cirrhosis • Cholangiocarcinoma • Pancreatic cancer Hepatocellular dysfunction • Hepatitis • Cirrhosis • Sepsis ___________________________________________________________________ Conjugated Hyperbilirubinemia (elevated direct bilirubin) ___________________________________________________________________ DDx of Conjugated HyperbilirubinemaDDx of Conjugated Hyperbilirubinema Extrahepatic cholestasis (biliary obstruction) • Choledocholithiasis • Cholangitis • Primary sclerosing cholangitis • Primary biliary cirrhosis • Pancreatitis • Malignancy - Pancreatic, Cholangiocarcinoma • Biliary tract strictures (trauma, post-ERCP) • Liver flukes Intrahepatic cholestasis • Most causes of transaminitis can potentially also result in conjugated hyperbiliribinemia 62 Gastroenterology The Short List 1. Choledocholithiasis 2. Cholangitis 3. Pancreatitis 4. Pancreatic cancer The Short List 1. Cirrhosis 2. Hemolysis 3. Gilbert’s On labs
___________________________________________________________________ Unconjugated Hyperbilirubinemia (elevated indirect bilirubin) ___________________________________________________________________ DDx of Unconjugated HyperbilirubinemaDDx of Unconjugated Hyperbilirubinema Increased bilirubin production • Hemolysis Impaired bilirubin conjugation • Cirrhosis • Crigler-Najjar syndrome • Gilbert’s syndrome • Wilson’s disease • Hyperthyroidism Impaired hepatic bilirubin uptake • Congestive heart failure ___________________________________________________________________ Hypoalbuminemia ___________________________________________________________________ DDx of HypoalbuminemiaDDx of Hypoalbuminemia Most Common • Malnutrition (decreased intake) • Cirrhosis (decreased production) • Nephrotic syndrome (increased loss) Other • Protein losing enteropathy (increased loss of albumin from increased permeability of GI tract due to mucosal disease): o Inflammatory bowel disease o Pseudomembranous colitis o Gastroenteritis o Gastritis o Celiac disease o GI malignancy o Post-chemotherapy 63 Gastroenterology Note Albumin is a negative acute phase reactant, meaning that it will be low in in- flammatory states. On labs
___________________________________________________________________ Elevated Amylase ___________________________________________________________________ DDx of Elevated AmylaseDDx of Elevated Amylase Pancreatic • Acute Pancreatitis • Chronic Pancreatitis • Pancreatic tumor • Trauma • Surgery • ERCP Other GI disease • Acute cholecystitis • Duodenal ulcer • Bowel obstruction • Bowel infarction • Appendicitis • Liver disease • Severe gastroenteritis • Celiac disease Neoplastic • Solid tumors of the lung, esophagus, thymus, breast, ovary, & prostate Gynecologic • Ruptured ectopic pregnancy • Pelvic inflammatory disease • Ovarian cysts • Pregnancy Other • DKA • HIV • Renal Failure • Alcoholism • Drug-induced • Idiopathic ___________________________________________________________________ Elevated Lipase ___________________________________________________________________ DDx of Elevated LipaseDDx of Elevated Lipase Pancreatic • Acute pancreatitis • Chronic pancreatitis • Pancreatic tumor Other GI disease • Acute cholecystitis • Duodenal ulcer • Bowel obstruction • Bowel infarction • Celiac disease Other • DKA • HIV • Drug-induced • Idiopathic 64 Gastroenterology On labs
On history/physical: • Lymphadenopathy………………………... On labs: • Leukocytosis……………………………… • Lymphocytosis…………………………… • Neutropenia................................................. • Anemia……………………………………. • Hemolytic Anemia………………………… • Thrombocytopenia…………...…………… • Neutropenia………………….……………. • Pancytopenia……………………………… • Coagulopathy……………………………... • Hypercoagulability/Thrombophilia.....…… • Elevated LDH……………..……………… • Elevated D-dimer…………………………. • Iron overload……………………………… Chapter 5 Hematology Overview of Topics
66 Hematology DDx of LymphadenopathyDDx of Lymphadenopathy Infectious Bacterial: Localized: • Strep pharyngitis • Bartonella (cat scratch disease) • Chancroid Generalized: • Tuberculosis • Secondary syphilis • Lyme disease • Lymphogranuloma venereum Viral: • HIV • EBV • CMV • HSV • Hepatitis B • Measles/Mumps/Rubella Fungal: • Histoplasmosis • Coccidioidomycosis • Cryptococcosis Protozoal: • Toxoplasmosis • Leishmaniasis The Short List - Generalized Lymphadenopathy 1. Leukemia 2. Lymphoma 3. Metastatic solid tumor 4. Infectious Mononucleosis 5. HIV 6. Tuberculosis ____________________________________________________________________________________________________________________________________________________________________ Lymphadenopathy ____________________________________________________________________________________________________________________________________________________________________ DDx of Lymphadenopathy (continued)DDx of Lymphadenopathy (continued) Neoplastic • Lymphoma • Leukemia • Metastatic disease Rheumatologic • SLE • Rheumatoid arthritis • Sarcoidosis Drugs • Drug reactions (ie. phenytoin) • Serum sickness
________________________________________________________________________ Leukocytosis ________________________________________________________________________ DDx of LeukocytosisDDx of Leukocytosis Infectious • Any infection (bacterial, viral, fungal, or other) Rheumatologic • Any rheumatological disease Neoplastic • Any neoplastic condition GI • Pancreatitis • Inflammatory bowel disease • Other bowel inflammation (ie. colitis, appendicitis, diverticulitis) Drugs • Steroids Tissue necrosis • Myocardial infarction • Pulmonary infarct from embolism • Bowel ischemia • Myositis • Trauma • Burns ________________________________________________________________________ Lymphocytosis ________________________________________________________________________ DDx of LymphocytosisDDx of Lymphocytosis Neoplastic • Acute lymphoblastic leukemia (ALL) • Chronic lymphocytic leukemia (CLL) • Lymphoma • Thymoma Infectious Viral: • Infectious mononucleosis (EBV) • CMV • HIV Bacterial: • Tuberculosis • Syphilis • Toxoplasmosis Other • Rheumatoid arthritis • Hyperthyroidism • Drug-induced • Cigarette smoking • Post-splenectomy 67 Hematology The Short List - Leukocytosis 1. Infection 2. Rheumatological disorder 3. Leukemia 4. Steroids 5. Tissue necrosis
DDx of NeutropeniaDDx of Neutropenia Infectious • Any infection Neoplastic • Leukemia • Lymphoma Drug Induced • Chemotherapy • DMARDs • Thionamides (ie. PTU) • Clozapine Nutritional • Alcoholism • Illicit drugs • Vitamin B12 deficiency • Folate deficiency Rheumatologic • SLE Other • Transfusion reaction • Hypersplenism 68 Hematology The Short List - Neutropenia 1. Chemotherapy 2. Alcoholism 3. Other drugs Definitions • Neutropenia is defined as a low absolute neutrophil count (ANC). Mild neutropenia corresponds to an ANC between 1000 and 1500/ microL, moderate between 500 and 1000/microL, and severe with less than 500/microL. The risk of infection begins to increase at an ANC below 1000/microL. • Leukopenia refers to a low total white blood cell count that may be due to any cause; however, almost all leukopenic patients are neutro- penic since the number of neutrophils is so much larger than the number of lymphocytes. • Agranulocytosis literally means the absence of granulocytes. It is often a term used synonymously with pancytopenia, although the term is also sometimes incorrectly used to indicate neutropenia (ie, ANC less than 500/microL). Noteworthy • Neutropenia is most commonly encountered in patients on chemotherapy, often at its worst around day 10 post-chemo. • It is crucial that all neutropenic patients be monitored for fever, in which case they would be diagnosed with febrile neutropenia. • Febrile neutropenia is a medical emergency that requires immediate therapy with antibiotics, whereas neutropenia alone without fever does not necessarily need to be treated with antibiotics. ____________________________________________________________________________________________________________________________________________________________________ Neutropenia ____________________________________________________________________________________________________________________________________________________________________
DDx of AnemiaDDx of Anemia Microcytic (MCV<80) • Iron Deficiency (blood loss or dietary deficiency) • Anemia of Chronic Disease (malignancy, inflammation, infection; late in disease) • Thalassemia • Sideroblastic Anemia • Lead Poisoning Normocytic (MCV 80 – 100) • See following page Macrocytic (MCV >100) • Folate deficiency • Vitamin B12 deficiency • Alcohol abuse • Liver Disease • Reticulocytosis • Myelodysplastic syndromes (MDS) • Hypothyroidism • Multiple myeloma • Drug-induced anemia: o Hydroxyurea o Methotrexate o Azathioprine 69 Hematology The Short List - Anemia DDx of AnemiaDDx of Anemia Microcytic Anemia • Iron deficiency • Anemia of chronic disease Normocytic Anemia • Blood loss • Anemia of chronic disease • Hemolysis Macrocytic Anemia • Alcohol abuse • Liver disease Contrary to what is commonly taught in most medical schools, B12 and folate deficiency are quite rare causes of macrocytic anemia in developed nations in comparison to alcohol and liver disease which are much more common. ____________________________________________________________________________________________________________________________________________________________________ Anemia ____________________________________________________________________________________________________________________________________________________________________
Differential Diagnosis of Normocytic AnemiaDifferential Diagnosis of Normocytic Anemia Low/Normal Reticulocytes General: • Acute blood loss • Anemia of chronic disease (seen early in disease processes where there is underlying inflammation) Bone Marrow Failure: • MDS • Aplastic Anemia Bone Marrow Infiltration: • Leukemia • Lymphoma • Multiple Myeloma • Metastatic tumor • Granulomatous disease Organ failure: • Cirrhosis • Chronic Kidney Disease • Hypothyroidism • Adrenal insufficiency DDx of Normocytic AnemiaDDx of Normocytic Anemia High Reticulocytes General: • Blood Loss Hemolysis: • Micorangiopathic Hemolytic Anemia (MAHA): o Hemolytic Uremic Syndrome (HUS) o Thrombotic Thrombocytopenic Purpura (TTP) o Disseminated Intravascular Coagulation (DIC) • Autoimmune Hemolytic Anemia • Traumatic Hemolysis Hemoglobinopathies: • Sickle cell disease Membranopathies: • Spherocytosis • Elliptocytosis Enzymopathies: • G6PD Deficiency • Pyruvate Kinase Deficiency 70 Hematology ____________________________________________________________________________________________________________________________________________________________________ Anemia (continued) ____________________________________________________________________________________________________________________________________________________________________
DDx of HemolysisDDx of Hemolysis Intravascular RBC destruction • Micorangiopathic Hemolytic Anemia (MAHA): o Hemolytic Uremic Syndrome (HUS) o Thrombotic Thrombocytopenic Purpura (TTP) o Disseminated Intravascular Coagulation (DIC) • Autoimmune hemolytic anemia (AIHA) • Traumatic hemolysis: o Hypertensive emergency o Artificial heart valve • Transfusion reactions • Scleroderma renal crisis Intrinsic RBC defects Hemoglobinopathies: • Sickle cell disease • Thalassemia Membranopathies: • Spherocytosis • Elliptocytosis Enzymopathies: • G6PD Deficiency • Pyruvate Kinase Deficiency 71 Hematology Hemolysis Workup 1st line investigations for hemolysis: • Markers of RBC hemolysis: o Elevated LDH o Elevated indirect bilirubin o Low haptoglobin • Peripheral blood smear: o Markers of hemolysis on smear are schistocytes and spherocytes o Spherocytes are seen in warm autoimmune hemolytic anemia o Schistocytes are seen in most other causes of hemolytic anemia, particularly microangiopathic hemolytic anemias (MAHAs) such as HUS-TTP and DIC. 2nd line investigations for hemolysis: • DAT (aka. Coombs test): o Positive in autoimmune hemolytic anemia o This test does not need to be ordered routinely in workup of hemo- lysis unless there is a strong initial suspicion for autoimmune hemolytic anemia ____________________________________________________________________________________________________________________________________________________________________ Hemolytic Anemia ____________________________________________________________________________________________________________________________________________________________________ The Short List - Hemolysis 1. HUS-TTP 2. DIC 3. Autoimmune hemolytic anemia 4. Transfusion reaction
DDx of ThrombocytopeniaDDx of Thrombocytopenia Decreased production Neoplastic: • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic syndrome • Metastatic disease Infectious: • Sepsis • Tuberculosis • HIV • Infectious mononucleosis Drug induced: • Chemotherapy • Alcohol Nutritional deficiencies: • Folate • B12 Other: • Liver disease DDx of ThrombocytopeniaDDx of Thrombocytopenia Increased destruction • Heparin Induced Thrombocytpenia (HIT) • Hemolytic-Uremic Syndrome (HUS) • Thrombotic Thrombocytopenic Purpura (TTP) • Disseminated Intravascular Coagulation (DIC) • Idiopathic Thrombocytopenic Purpura (ITP) • Antiphospholipid syndrome (APS) • SLE Sequestration • Splenomegaly 72 Hematology The Short List - Thrombocytopenia 1. Sepsis 2. Alcoholism 3. Liver disease 4. Splenomegaly 5. HIT 6. HUS/TTP, DIC 7. ITP ____________________________________________________________________________________________________________________________________________________________________ Thrombocytopenia ____________________________________________________________________________________________________________________________________________________________________
DDx of PancytopeniaDDx of Pancytopenia Primary bone marrow etiologies Drugs & Toxins: • Chemotherapy • Radiation • Alcohol • NSAIDs • Sulfonamides (TMP-SMX) • Antiepileptic drugs (felbamate) • Chloramphenicol • Cimetidine • Benzene Infectious: • Hepatitis • HIV • EBV • Parvovirus B19 Neoplastic: • Leukemia (particularly acute leukemias) • Myelodysplastic syndrome • Myelofibrosis • Metastases from solid tumor to marrow DDx of PancytopeniaDDx of Pancytopenia Systemic disease with secondary bone marrow effects Immune disorders: • SLE • Sjogren’s syndrome • Graft versus host disease Nutritional deficiencies: • Vitamin B12 • Folate Other: • Sepsis • Splenomegaly • Pregnancy Congenital diseases: • Fanconi’s anemia • Storage diseases (Gaucher’s, Niemann-Pick) 73 Hematology Notes: • Aplastic anemia is characterized by diminished or absent hematopoietic precursors in the bone marrow, most often due to injury to the pluripotent stem cell. • The designation "aplastic anemia" is a somewhat of a misnomer because the disorder is defined as pancytopenia rather than anemia alone. ____________________________________________________________________________________________________________________________________________________________________ Pancytopenia ____________________________________________________________________________________________________________________________________________________________________
DDx of CoagulopathyDDx of Coagulopathy Increased INR (extrinsic pathway) • Warfarin • Vitamin K deficiency • Liver disease (acute liver failure or cirrhosis) • Factor VII deficiency/Factor VII inhibitor • Rat poison Increased PTT (intrinsic pathway) • Heparin • Hemophilia A or B • Deficiency or inhibitor of intrinsic factors • Lupus anticoagulant • Von Willebrand’s disease Increased INR & PTT • Liver disease (acute liver failure or cirrhosis) • Disseminated intravascular coagulation (DIC) • Combined heparin and warfarin • Factor II, V, or X inhibitors 74 Hematology Notes - Nomenclature • Coagulopathy and bleeding diathesis are often used interchangeably to describe an unusual susceptibility to bleeding (hemorrhage) due to a de- fect in the system of coagulation. However, the term bleeding diathesis often includes reference to underlying platelet dysfunction, whereas the term coagulopathy is more specific to defects in INR & PTT. ____________________________________________________________________________________________________________________________________________________________________ Coagulopathy/Bleeding Diathesis ____________________________________________________________________________________________________________________________________________________________________
DDxof Hypercoagulability /ThrombophiliaDDxof Hypercoagulability /Thrombophilia Acquired Antiphospholid Antibody Syndrome (APS): • Lupus Anticoagulant • Anticardiolipin Antibodies • Beta2-glycoprotein-I Antibodies Other hematological causes: • Heparin induced thrombocytopenia (HIT) • Disseminated intravascular coagulation (DIC) • Paroxysmal nocturnal hemoglobinuria (PNH) • Polycythemia vera • Essential thrombocytosis Systemic disease: • Malignancy • Inflammatory bowel disease • Nephrotic syndrome • HIV/AIDS Drugs: • Oral contraceptive pills (OCPs) • Hormone replacement therapy (HRT) Other: • Pregnancy • Immobilization • Surgery/Trauma DDx of Hypercoagulability /ThrombophiliaDDx of Hypercoagulability /Thrombophilia Inherited Always detectable: • Factor V Leiden mutation • Prothrombin gene mutation Must be off anticoagulation for detection: • Antithrombin deficiency • Protein C & S deficiency 75 Hematology The Short List - Thrombophilia 1. Immobilization/Surgery/Trauma 2. Malignancy 3. OCPs 4. APS 5. HIT 6. Inherited thrombophilias ____________________________________________________________________________________________________________________________________________________________________ Hypercoagulability/ Thrombophilia ____________________________________________________________________________________________________________________________________________________________________
76 Hematology Notes • Thrombophilia is a hereditary or acquired predisposition to develop blood clots. These blood clots can be either arterial or venous thrombosis. • Note that the differential on the previous page is for venous thrombosis. Causes of both venous and arterial thrombosis are seen in: Major Causes of Arterial & Venous Thrombosis • Antiphospholipid Syndrome (APS) • Heparin induced thrombocytopenia (HIT) • Disseminated intravascular coagulation (DIC) • Paroxysmal nocturnal hemoglobinuria (PNH) ____________________________________________________________________________________________________________________________________________________________________ Hypercoagulability/ Thrombophilia ____________________________________________________________________________________________________________________________________________________________________ Lab Workup - Hypercoagulability • Routine workup of a new diagnosis of thrombosis without obvious precipi- tant may include the following: o Lupus anticoagulant & anticardiolipin o Factor V Leiden o Prothrombin gene mutation o Antithrombin levels o Protein C& S levels • Antithrombin levels measured in the blood are decreased when there is thrombosis present or when the patient is given heparin. Protein C & S lev- els are decreased by warfarin. • Therefore, when measuring the levels of Antithrombin, Protein C, and Pro- tein S, it is necessary that the patient be off anticoagulation and that there be no evidence of thrombosis. • Furthermore, it is important to note that antithrombin and protein C&S are acute phase reactants, hence can be elevated during acute illness.
______________________________________________________________________________ Elevated LDH (Lactate Dehydrogenase) ____________________________________________________ DDx of Elevated LDHDDx of Elevated LDH Cell Lysis • RBC Hemolysis • Tumor Lysis Syndrome • Rhabdomyolysis • Acute liver injury • Lymphoma (rapid cell turnover) Infectious • Pneumocystis jiroveci (PJP) Cardiac • Myocardial Infarction Obs-Gyn • Dysgerminoma ______________________________________________________________________________ Elevated D-dimer ____________________________________________________ 77 Hematology Notes • LDH is an intracellular enzyme found in most cells, involved in the Krebs cycle.. • Any injury leading to cell breakdown or lysis will release LDH into the bloodstream, and hence can theoretically account for an elevation in LDH levels. • LDH is a very non-specific enzyme found to be elevated in many condi- tions, however the levels are often significantly elevated when there is un- derlying cell lysis. • When levels of LDH are seen in the thousands, you should particularly investigate and aim to rule out RBC hemolysis, tumor lysis, rhadbomyoly- sis, acute liver injury, and lymphoma. Notes: • The utility of ordering a D-dimer test is limited to excluding DVT or PE in patient at low probability as per their Well’s score. • This is due to the fact that D-dimer is extremely sensitive for DVT and/or PE, with a sensitivity between 85 and 95% based on which assay the lab at your facility uses. • The other major use in ordering a D-dimer is when you are suspecting DIC. DDx of Elevated D-dimerDDx of Elevated D-dimer Thromboembolic disease Any venous or arterial thrombus, particularly: • Deep venous thrombosis • Pulmonary embolism Cardiac • Myocardial infarct • Congestive heart failure • Atrial fibrillation Renal • Acute renal failure • Chronic kidney disease • Nephrotic syndrome Other • Severe infection/sepsis • Inflammation • Malignancy • Liver disease • Surgery • Trauma • Pregnancy
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
The Complete Guide to Differential Diagnoses
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The Complete Guide to Differential Diagnoses

  • 1. Sam Gharbi, MD Understanding Internal Medicine A complete Guide to Differential Diagnoses
  • 2. written by Sam Gharbi, MD Understanding Internal Medicine Differential Diagnoses
  • 3. 2 Disclaimer Extensive effort has been exerted in order to make this book as accurate as possible. However, the accuracy and completeness of the information provided cannot be guaranteed. This book is to be used as an educational guide only, and healthcare professionals should use sound clinical judgement and individualize therapy to each specific patient care situation. The author makes no claims whatsoever, expressed or implied, about the authenticity, accuracy, reliability, com- pleteness, or timeliness of the material presented in this book. In no event shall the author be liable to any party for indirect, direct, special, incidental, or consequential damages, including but not limited to lost profits arising out of the use of this book, even if the author has been advised of such damage. By having read the above, or by use of this book, be it partially or in its entirety, you have explicitly consented your agreement to the above disclaimer.
  • 4. 3 © Copyright 2013 Sam Gharbi. All Rights Reserved.
  • 5. 4 INTRODUCTION The differential diagnosis is at the core of medicine. Without a good differential to start off with, your approach to the history, physical, and investigations will be incomplete. In essence, your entire assessment of the patient begins with your differential diagnosis in regards to the presenting complaint. This document started as notes that I had made for myself over the years during the course of my medical training, and ulti- mately has evolved into an e-book that is a collection of differential diagnoses that address a variety of medical problems. The differentials outlined in this e-book cover the topic of internal medicine, although are generally applicable to most fields of medi- cine. Topic exclusions notably include obs/gyn, pediatrics, and psychiatry, as they are unfortunately outside the scope of my ex- pertise and practice. Ultimately this e-book is meant to be a user friendly educational guide with the purpose of bestowing a general framework for medical learners. It is not meant to be a clinical reference guide to be used for medical decision making, nor is it meant to be a complete list of every different possible pathology that may be contributing to a differential diagnosis. I hope that you, the reader, find this e-book to be a helpful educational resource. Sincerely, Sam Gharbi Internal Medicine Physician MD, CM, FRCPC
  • 6. 5 Please feel free to click on the icon below which will enable you to anonymously message me with feedback regarding the e-book & how it can be further improved. Your feedback is greatly appreciated. FEEDBACK
  • 7. 6 Click on the icon below to take notes & save them within this e-book MY NOTES
  • 8. On history: • Chest pain…………………………………. • Syncope…………………………………… • Palpitations……………………………….. On physical: • Hypertension……………………………..... • Hypotension/Shock………………………... • Bradycardia/Tachycardia............................... • Abnormal Heart Sounds............................... • Peripheral Edema……………………......... On labs: • Elevated Troponins………………………............ On ECG: • T Wave Inversions/ST changes................... • Tachyarrhythmias………………………… • Conduction Block………………………… • Bundle Branch Block…………………….. • Prolonged QT Segment…………………… Overview of Topics Chapter 1 Cardiology Reviewed by Dr. Richard Vandegriend
  • 9. DDx of Chest PainDDx of Chest Pain Cardiac • Coronary Artery Disease • Acute Coronary Syndromes (Myocardial Infarct) • Aortic Dissection • Myopericarditis Pulmonary • Pneumonia • Pulmonary Embolism • Pneumothorax • Pleuritis • Pulmonary Hypertension GI • Gastroesophageal reflux disease (GERD) • Esophagitis • Esophageal spasm • Esophageal dissection (Mallory Weiss syndrome) • Esophageal rupture (Boerhave’s syndrome) • Peptic Ulcer Disease • Biliary Disease • Pancreatitis Musculoskeletal • Costochondritis • Osteoarthritis Other • Herpes zoster • Anxiety 8 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Chest Pain ____________________________________________________________________________________________________________________________________________________________________ The Short List - Chest Pain 1. Coronary Artery Disease (CAD) 2. Acute Coronary Syndrome (ACS) 3. Aortic Dissection 4. Pericarditis 5. Gastroesophageal reflux disease (GERD) 6. Costochondritis On history
  • 10. DDx of SyncopeDDx of Syncope Cardiovascular (Cardiogenic) • Arrhythmia • Valvular heart disease (particularly AS & MS) • Hypertrophic cardiomyopathy • Pericardial tamponade • Pulmonary embolism • Pulmonary hypertension Neurologic (Neurogenic) • Seizure (technically not syncope) • TIA/Stroke Neurocardiogenic • Vasovagal syncope • Carotid sinus hypersensitivity • Situational syncope (cough, deglutition, defecation, & micturition syncope) Orthostatic • Hypovolemia • Drug induced • Autonomic neuropathy (from diabetes, alcohol, renal failure, Parkinson’s & amyloidosis) Other (technically not syncope) • Hypoglycemia • Anemia • Hypoxia • Psychogenic 9 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Syncope ____________________________________________________________________________________________________________________________________________________________________ The Short List - Syncope 1. Arrhythmia 2. Aortic Stenosis 3. TIA/Stroke 4. Vasovagal syncope 5. Orthostatic hypotension 6. Hypoglycemia On history
  • 11. DDx of PalpitationsDDx of Palpitations Cardiac • Premature Ventricular Contractions (PVCs) • Premature Atrial Contractions (PACs) • Any Tachyarrhythmia • Pacemaker Endocrine • Hyperthyroidism • Hypoglycemia • Pheochromocytoma Drugs Prescription Drugs: • Sympathomimetics • Anticholinergics • Beta blocker withdrawal Other Drugs: • Nicotine • Caffeine • Cocaine • Amphetamines Psychiatric • Panic attack • Generalized anxiety disorder • Depression • Somatization Other • Stress • Exercise • Fever • Anemia • Pregnancy 10 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Palpitations ____________________________________________________________________________________________________________________________________________________________________ The Short List - Palpitations 1. Premature Ventricular Contractions (PVCs) 2. Tachyarrhythmias (ie. AFib, AFlutter, SVT) 3. Hyperthyroidism 4. Hypoglycemia 5. Drugs 6. Panic Attacks On history
  • 12. DDx of HypertensionDDx of Hypertension Renal • Renal parenchymal disease o Chronic kidney disease o Glomerulonephritis o Polycystic kidney disease • Renovascular disease o Renal artery stenosis Endocrine • Hypo and Hyperthyroidism • Hypercalcemia • Hyperaldosteronism • Cushing’s disease • Pheochromocytoma Drugs Medical Drugs: • Oral contraceptives (OCPs) • NSAIDS • Steroids Illicit Drugs: • Chronic alcohol use & withdrawal • Cocaine • Amphetamines Other • Obstructive sleep apnea (OSA) • Coarctation of the aorta • Polycythemia vera • Pre-eclampsia & eclampsia 11 Cardiology ____________________________________________________________________________________________________________________________________________________________________ Hypertension ____________________________________________________________________________________________________________________________________________________________________ The Short List - Hypertension 1. Essential Hypertension (most common) 2. Chronic kidney disease 3. Thyroid disease 4. Hypercalcemia 5. Drugs - OCPs/NSAIDs/Steroids 6. OSA Hypertension Workup • Routine workup for hypertension often involves bloodwork, including CBC, electrolytes, creatinine & BUN, as well as ECG and chest X-ray • In patients suspected of having a secondary cause of hypertension, depend- ing on history and physical findings, further workup may involve any of the following: o TSH o Serum calcium o Plasma Aldosterone to Renin ratio (for hyperaldosteronism) o 24 hour urine catecholamines (for pheochromocytoma) o Urinalysis (looking for proteinuria or casts in glomerulonephritis) o Overnight oximetry (for OSA) On physical
  • 13. ______________________________________________________________________________ Hypertension + Tachycardia ______________________________________________________________________________ DDx of HTN + TachycardiaDDx of HTN + Tachycardia Endocrine • Thyrotoxicosis • Pheochromocytoma Drugs • Alcohol withdrawal • Cocaine/Amphetamine toxicity Other • Neuroleptic Malignant Syndrome (NMS) • Malignant Hyperthermia • Serotonin Syndrome ______________________________________________________________________________ Hypotension/Shock ______________________________________________________________________________ 12 Cardiology NOTE: The differential diagnosis for hypotension is almost identical to that of shock, except for the fact that drugs (both medical and illicit) are a major contributor in the case of hypotension but rarely cause shock unless in cases of overdose. On physical DDx of Hypotension/ShockDDx of Hypotension/Shock Hypovolemic • Hemorrhage • GI tract loss (vomiting, diarrhea) • Urinary tract loss (diabetes insipidus) • Third spacing (pancreatitis, bowel obstruction) • Skin loss (severe burns) Cardiogenic • Acute myocardial infarct & its complications • End-stage cardiomyopathy • Hypertrophic obstructive cardiomyopathy (HOCM) • Severe valvular dysfunction Obstructive • Cardiac tamponade • Massive pulmonary embolism • Tension pneumothorax • Cor pulmonale Distributive • Septic shock • Anaphylactic shock • Neurogenic shock • Adrenal crisis or adrenal insufficiency Drugs • Any BP lowering agent (ie. beta blockers, CCBs)
  • 14. ________________________________________________________________________ Bradycardia ________________________________________________________________________ DDx of BradycardiaDDx of Bradycardia Cardiac • Bradyarrhythmias o Sinus Bradycardia o Sick Sinus Syndrome • Conduction block • Myocardial Infarct Drugs • Beta blockers • Calcium channel blockers • Digoxin • Antiarrhythmic drugs Endocrine • Hypothyroidism • Hypothermia Metabolic • Hyperkalemia • Hypokalemia Infiltrative • Sarcoidosis • Amyloidosis • Hemochromatosis Infectious • Endocarditis ________________________________________________________________________ Sinus Tachycardia ________________________________________________________________________ DDx of Sinus TachycardiaDDx of Sinus Tachycardia Cardiac • Myocardial infarction • Congestive Heart failure Pulmonary • Pulmonary Embolism • Chronic pulmonary disease • Hypoxia Endocrine • Hyperthyroidism • Pheochromocytoma Drugs • Beta-agonists (ie. ventolin) • Alcohol withdrawal • Nicotine • Caffeine • Cocaine • Amphetamines Psychiatric • Panic attacks • Generalized anxiety disorder Other • Pain • Fever • Sepsis • Hypovolemia • Hypotension and shock • Anemia • Postural Tachycardia Syndrome (POTS) 13 Cardiology On physical
  • 15. ________________________________________________________________________ Abnormal Heart Sounds - S1 & S2 ________________________________________________________________________ DDx of Abnormal Heart SoundsDDx of Abnormal Heart Sounds Loud S1 • Mitral stenosis • Tricuspid stenosis • Mitral valve prolapse (MVP) • Atrial & Ventricular septal defects • Atrial myxoma • Tachycardia • Short PR interval Soft S1 • Severe Mitral stenosis • Mitral regurgitation • Aortic regurgitation (acute) • Aortic stenosis (severe) • Dilated cardiomyopathy • Left bundle branch block (LBBB) • Long PR interval Fixed splitting of S2 • Atrial septal defect • Severe right ventricular failure Paradoxical splitting of S2 Prolonged left ventricular ejection time: • Aortic stenosis • Aortic regurgitation • Myocardial infarct • Hypertension • Hypertrophic obstructive cardiomyopahty Delayed left ventricular activation: • Left bundle branch block • Wolffe-Parkinson-White syndrome ________________________________________________________________________ Abnormal Heart Sounds - S3 & S4 ________________________________________________________________________ DDx of Abnormal Heart SoundsDDx of Abnormal Heart Sounds S3 gallop • Congestive Heart Failure • Mitral regurgitation • Tricuspid regurgitation • Aortic regurgitation • Thyrotoxicosis • Pregnancy S4 gallop • Aortic Stenosis • Myocardial infarct (during acute phase) • Hypertension • Hypertrophic cardiomyopathy • Pulmonary Hypertension 14 Cardiology On physical
  • 16. ________________________________________________________________________ Bilateral Peripheral Edema ________________________________________________ DDx of Bilateral Peripheral EdemaDDx of Bilateral Peripheral Edema Increased capillary hydraulic pressure • Congestive Heart Failure (CHF) • Pregnancy • Drugs: o NSAIDs o Calcium Channel Blockers o Estrogens (OCPs, HRT) Hypoalbuminemia • Nephrotic syndrome • Cirrhosis • Malnutrition • Protein-losing enteropathy (ie. colitis) Endocrine disease • Hypothyroidism • Grave’s disease ________________________________________________________________________ Unilateral Peripheral Edema ________________________________________________ DDx of Unilateral Peripheral EdemaDDx of Unilateral Peripheral Edema Increased capillary permeability • Trauma (muscle strain, tear, or injury) • Ruptured Baker’s cyst (popliteal cyst) • Cellulitis • Arthritis • Allergic reactions • Burns Increased interstitial oncotic pressure • Deep vein thrombosis (DVT) • Venous insufficiency • Lymphedema/Lymphatic obstruction 15 Cardiology On physical
  • 17. DDx of Elevated TroponinsDDx of Elevated Troponins Cardiac • Myocardial infarct • Myocarditis • Endocarditis • Aortic Dissection • Congestive heart failure • Aortic stenosis • Cardioversion • Cardiac trauma • Other cardiomyopathy Pulmonary • Pulmonary embolism • Pulmonary hypertension Renal • Renal failure • Hemodialysis Infiltrative • Sarcoidosis • Amyloidosis • Hemochromatosis Other • Sepsis • Stroke • Subarachnoid hemorrhage 16 Cardiology Notes Troponins originate from heart muscle, and elevated levels often indicate underly- ing damage to cardiac tissue in the form of ischemia or infarct. Overall, there are 3 underlying mechanisms for an elevation in troponins: 1. Primary myocardial infarct • This is usually in the form of underlying atherosclerosis and/or plaque rupture 2. Secondary myocardial infarct • This is in the form of supply-demand mismatches from systemic causes such as hypertensive emergency or anemia 3. Heart Strain • This is actually not infarct, but cardiac strain causing release of troponins. The rise in troponins is usually less marked in these situations, such as CHF, sepsis, intracranial hemorrhage, etc. On labs __________________________________________________________________________________________________________________________________________________________________ Elevated Troponins __________________________________________________________________________________________________________________________________________________________________ The Short List - Elevated Troponins • Myocardial Infarct • Myocarditis • Aortic Dissection • Pulmonary embolism • Renal failure • Sepsis
  • 18. ________________________________________________________________________ T Wave Inversions ________________________________________________________________________ DDx of Ischemic ECG ChangesDDx of Ischemic ECG Changes T wave inversion Cardiac etiologies: • Myocardial ischemia or infarct • Cardiomyopathy • Mitral Valve prolapse • Ventricular hypertrophy • Bundle Branch Block • Post-tachycardia Other etiologies: • Intracranial bleed • Digoxin toxicity • Electrolyte abnormalities (ie. Hypokalemia) ________________________________________________________________________ ST Segment Changes ________________________________________________________________________ DDx of Ischemic ECG ChangesDDx of Ischemic ECG Changes ST depression Cardiac etiologies: • NSTEMI • Posterior STEMI (ST depression in V1-V2) • Post-MI • Ventricle Hypertrophy with strain • Bundle Branch Block • Wolff-Parkinson-White syndrome Other etiologies: • Digoxin effect (scooping) • Hypokalemia • Hypomagnesemia ST elevation Cardiac etiologies: • STEMI • LV aneurysm • Left Bundle Branch Block • Coronary Spasms (Prinzmetal’s Angina) • Pericarditis • Myocarditis Other etiologies: • Pulmonary embolism • Hypothermia 17 Cardiology On ECG
  • 19. 18 Cardiology __________________________________________________________________________________________________________________________________________________________________ Tachyarrhythmias - Narrow Complex (QRS <120ms) __________________________________________________________________________________________________________________________________________________________________ On ECG DDx of Narrow Complex Tachyarrhythmias (QRS < 120 ms)DDx of Narrow Complex Tachyarrhythmias (QRS < 120 ms) Regular rhythm With P Waves: • Sinus Tachycardia • Atrial Tachycardia • Atrial Flutter • AVRT Without P Waves: • AVNRT Irregular rhythm With P Waves: • Atrial Tachycardia with variable block • Atrial Flutter with variable block • Multifocal Atrial Tachycardia (MAT) Without P Waves: • Atrial Fibrillation Narrow Complex Tachyarrhythmias (QRS<120 ms) With P waves • Sinus Tachycardia • Atrial Flutter • AVRT Without P waves • AVNRT Regular Rhythm Irregular Rhythm With P waves • Atrial Flutter with variable block • Multifocal Atrial Tachycardia (MAT) Without P waves • Atrial Fibrillation
  • 20. 19 Cardiology On ECG __________________________________________________________________________________________________________________________________________________________________ Tachyarrhythmias - Wide Complex (QRS >120 ms) __________________________________________________________________________________________________________________________________________________________________ DDx of Wide Complex Tachyarrhythmias (QRS >120 ms)DDx of Wide Complex Tachyarrhythmias (QRS >120 ms) Regular rhythm • Ventricular Tachycardia • SVT with aberrancy • Pacemaker arrhythmia • Artifact Irregular rhythm • Ventricular Fibrillation • Atrial Fibrillation with aberrancy Wide Complex Tachyarrhythmias (QRS>120 ms) Regular Rhythm Irregular Rhythm • Ventricular Tachycardia • SVT with aberrancy • Pacemaker arrhythmia • Artifact • Ventricular Fibrillation • Atrial Fibrillation with aberrancy
  • 21. DDx of Conduction BlockDDx of Conduction Block Cardiac • Coronary artery disease • Acute coronary syndrome (myocardial infarct) • Cardiomyopathy • Myocarditis • Endocarditis • Increased vagal tone • Congenital heart disease Metabolic • Hyperkalemia • Hypo or Hyperthyroidism Drugs • Beta blocker • Calcium channel blocker • Digoxin • Amiodarone Infiltrative • Infiltrative malignancy (ie. lymphoma) • Amyloidosis • Sarcoidosis • Tuberculosis Iatrogenic • Cardiac surgery • Catheter ablation 20 Cardiology On ECG __________________________________________________________________________________________________________________________________________________________________ Conduction Block (AV block) __________________________________________________________________________________________________________________________________________________________________ The Short List - Conduction Block • Coronary artery disease • Myocardial infarct • Cardiomyopathy • Congenital heart disease • Drugs
  • 22. ________________________________________________________________________ Right Bundle Branch Block ________________________________________________________________________ DDx of Right Bundle Branch BlockDDx of Right Bundle Branch Block Cardiac • Coronary artery disease • Myocardial infarct • Right heart failure (cor pulmonale) • Myocarditis • Cardiomyopathies • Hypertension Pulmonary • Pulmonary embolism Iatrogenic • Right heart catheterization Other • Hyperkalemia • Lenegre’s disease • Lev’s disease ________________________________________________________________________ Left Bundle Branch Block ________________________________________________________________________ DDx of Left Bundle Branch BlockDDx of Left Bundle Branch Block Cardiac • Coronary artery disease • Myocardial infarct • Congestive heart failure • Myocarditis • Cardiomyopathies • Hypertention • Valvular heart disease Other • Endocarditis • Hyperkalemia • Digoxin toxicity 21 Cardiology On ECG
  • 23. DDx of Long QT segmentDDx of Long QT segment Cardiac • Myocardial infarct Drugs • Antiarrhythmics • Antibiotics o Fluoroquinolones o Erythromycin o Azithromycin o Chloroquine • Antipsychotics o TCA o SSRIs o Haldol o Risperidone • Antihistamines • HIV protease inhibitors • Cocaine • Methadone Metabolic • Hypokalemia • Hypocalcemia • Hypomagnesemia • Hypothyroidism Congenital • Jervell & Lange-Nielsen syndrome • Romano-Ward syndrome • Idiopathic 22 Cardiology On ECG __________________________________________________________________________________________________________________________________________________________________ Prolonged QT Interval ________________________________________________________________________________________________________________________________________________________________ The Short List - Prolonged QT • Myocardial Infarct • Antiarrhtyhmics • Antibiotics • Antipsychotics • Antihistamines • Hypocalcemia
  • 24. On history: • Dyspnea………………………………….. • Cough……………………………………. • Hemoptysis………………………………. • Pleuritic pain……………………………... On physical: • Clubbing………………………………….. On imaging: • Pleural Effusions…………………………. • Interstitial Infiltrates……………............... • Bilateral Hilar Lymphadenopathy………... • Pulmonary Nodules………………………. • Cavitary Lung Lesions…………………… Chapter 2 Respirology Overview of Topics
  • 25. DDx of DyspneaDDx of Dyspnea Neuromuscular Neuromuscular disease: • Multiple Sclerosis • Myasthenia Gravis • Guillain Barre syndrome (GBS) • Amyotrophic Lateral Sclerosis (ALS) • Kyphoscoliosis Other: • Stroke • Spinal chord injury • Rib fractures Toxins • Salicylate poisoning • Organophosphate poisoning • Carbon monoxide poisoning Other • Anemia • Metabolic Acidosis • Increased abdominal girth (ie. ascites) • Anaphylaxis • Anxiety/Panic Attack 24 Respirology DDx of DyspneaDDx of Dyspnea Pulmonary Airway Obstruction: • COPD • Asthma • Bronchiectasis • Tumor • Foreign body Parenchymal Disease: • Pneumonia • Pulmonary Edema o Cardiogenic o Non-Cardiogenic (ALI/ARDS) • Intersitial Lung Disease (ILD) Pleural Disease: • Pleural Effusion • Pneumothorax Vascular: • Pulmonary Embolism • Pulmonary Hypertension • Pulmonary Hemorrhage • Vasculitis Cardiac • Coronary artery disease (anginal equivalent) • Congestive Heart Failure • Myocardial Infarction • Pericardial Tamponade The Short List - Acute Dyspnea 1. COPD/Asthma 2. Pneumonia 3. Pulmonary Embolism 4. Pneumothorax 5. CHF ___________________________________________________________________________________________________________________________________________________________________ Dyspnea (Shortness of Breath) ___________________________________________________________________________________________________________________________________________________________________ On history
  • 26. ________________________________________________________________________ Cough ________________________________________________________________________ DDx of CoughDDx of Cough Respiratory Infectious: • Upper respiratory tract infection (URTI) • Pneumonia Non-Infectious: • Postnasal drip • Asthma • Chronic Bronchitis • Bronchiectasis • Lung cancer GI • Gastroesophageal reflux (GERD) Drugs • ACE inhibitors ________________________________________________________________________ Hemoptysis ________________________________________________________________________ DDx of HemoptysisDDx of Hemoptysis Inflammatory • Chronic Bronchitis • Bronchiectasis • Cystic Fibrosis Infectious • Pneumonia • Lung abscess • Tuberculosis • Aspergilloma Neoplastic • Lung Cancer (usually primary) Cardiovascular • Pulmonary Embolism • Congestive Heart Failure • Mitral Stenosis Other • Wegener’s Granulomatosis • Goodpasture’s syndrome • Excessive anticoagulation • Arterio-Venous Malformation (AVM) 25 Respirology The Short List - Hemoptysis 1. Chronic Bronchitis 2. Bronchiectasis 3. Pulmonary Embolism 4. Pneumonia 5. Tuberculosis 6. Lung cancer On history
  • 27. _______________________________________________________________ Pleuritic Pain _______________________________________________________________ DDx of Pleuritic PainDDx of Pleuritic Pain Pulmonary • Pulmonary Embolism • Pneumothorax • Pneumonia • Viral pleurisy • Pleural effusion Cardiac • Pericarditis _______________________________________________________________ Clubbing _______________________________________________________________ DDx of ClubbingDDx of Clubbing Pulmonary • Lung cancer (primary or metastatic) • Interstitial lung disease (ILD) • Bronchiectasis • Cystic Fibrosis • Lung abscess • Tuberculosis Cardiac • Endocarditis • Atrial myxoma • Congenital heart disease GI • Inflammatory bowel disease (IBD) • Cirrhosis Other • Hyperthyroidism • Thalassemia 26 Respirology Definition • Pleuritic pain (or pleuritic chest pain) is due to inflammation of nerve endings of pain fibers in the pleura. • Pleuritic pain often has a stabbing quality that worsens with inspira- tion, and may be felt most anywhere in the chest. On history/physical
  • 28. DDx of Exudative Pleural EffusionsDDx of Exudative Pleural Effusions Infectious • Bacterial pneumonia • Tuberculosis • Viral pneumonia • Fungal infection • Parasitic infection Malignancy • Primary Lung Cancer • Metastases • Mesothelioma Respiratory • Pulmonary embolism Inflammatory • Rheumatoid arthritis (large effusion) • SLE (small effusion) • Wegener’s granulomatosis Gastrointestinal • Esophageal rupture • Pancreatitis • Abdominal abscess Other • Hemothorax • Post-CABG • Meigs’s syndrome • Drug induced (ie. amiodarone) DDx of Transudative Pleural EffusionsDDx of Transudative Pleural Effusions Most common • Congestive Heart Failure • Cirrhosis • Nephrotic syndrome • Constrictive Pericarditis Other (usually exudative) • Pulmonary embolism • Malignancy 27 Respirology On physical/imaging ___________________________________________________________________________________________________________________________________________________________________ Pleural Effusion ___________________________________________________________________________________________________________________________________________________________________
  • 29. DDx of Bilateral Interstitial InfiltratesDDx of Bilateral Interstitial Infiltrates Cardiogenic Pulmonary Edema • Congestive Heart Failure Non-Cardiogenic Pulmonary Edema • ALI • ARDS • Pulmonary embolism • Reperfusion pulmonary edema • Re-expansion pulmonary edema • Neurogenic pulmonary edema o Intracerebral hemorrhage o Subarachnoid hemorrhage o Intracranial surgery o Generalized seizures Diffuse Alveolar Hemorrhage • ARDS • Endocarditis (septic emboli) • Wegener’s granulomatosis • Goodpasture’s syndrome • Pulmonary Infarct • Trauma Infection • Any cause of pneumonia, be it bacterial, viral, or fungal can cause interstitial infiltrates, although special attention should be given to P. jiroveci (PJP, formerly called PCP) Malignancy • Any malignancy (primary or metastatic) • Lymphangitic carcinomatosis 28 Respirology The Short List - Lung Infiltrates 1. CHF 2. ALI/ARDS 3. Hemorrhage 4. Malignancy ___________________________________________________________________________________________________________________________________________________________________ Bilateral Interstitial Infiltrates ___________________________________________________________________________________________________________________________________________________________________ Notes: • Interstitial infiltrates can generally be described as opacification within the lung fields. • This opacification is due to an increase in density of matter at that loca- tion, and can be caused by any of the following: § Water (edema) § Blood (hemorrhage) § Pus (infection) § Tumor On imaging
  • 30. _______________________________________________________________ Bilateral Hilar Lymphadenopathy _______________________________________________________________ DDx of Bilateral Hilar LymphadenopathyDDx of Bilateral Hilar Lymphadenopathy Rheumatologic • Sarcoidosis Infectious • Tuberculosis • Fungal (ie. Histo, Coccidio) Neoplastic • Lymphoma • Lung cancer • Metastatic disease Other • Pneumoconioses o Silicosis o Berylliosis o Coal-worker’s pneumoconiosis • Prominent pulmonary artery or veins (Pseudo-hilar adenopathy) _______________________________________________________________ Pulmonary Nodules _______________________________________________________________ DDx of Pulmonary NodulesDDx of Pulmonary Nodules Benign • Infectious Granuloma: o Tuberculosis o Histoplasmosis o Coccidioidomycosis o Blastomycosis o Cryptococcus • Other Infections: o Bacterial Abscess o PJP o Aspergilloma • Benign Neoplasms: o Hamartoma o Lipoma o Fibroma • Inflammatory: o Rheumatoid nodule o Wegener’s granulomatosis Malignant • Brochogenic carcinoma • Metastatic 29 Respirology The Short List - Lung Nodules 1. Granuloma (TB) 2. Hamartoma 3. Cancer On imaging
  • 31. DDx of Cavitary Lung LesionsDDx of Cavitary Lung Lesions Infectious Bacterial: • Bacterial Pneumonia Cavitary lesions caused by bacterial pneumonia are also called pulmonary gangrene. • Endocarditis with septic emboli • Tuberculosis • Abscess Fungal: • Aspergillus • Histoplasma • Coccidoides • Mucor Rheumatologic • Wegener’s Granulomatosis • Rheumatic Arthritis • Sarcoidosis Neoplastic • Primary Lung Cancer • Metastatic Lung Cancer DDx of Cavitary Lung Lesions by SizeDDx of Cavitary Lung Lesions by Size Small Cavitary Lesions Large Cavitary Lesions • Endocarditis with septic emboli • Rheumatoid arthritis • Wegener’s granulomatosis • Lung cancer • Tuberculosis • Abscess • Lung cancer 30 Respirology On imaging ___________________________________________________________________________________________________________________________________________________________________ Cavitary Lung Lesions ___________________________________________________________________________________________________________________________________________________________________ The Short List - Cavitary Lesions 1. Lung cancer 2. Tuberculosis 3. Pneumonia 4. Endocarditis with septic emboli 5. Fungal
  • 32. General: • Acute Kidney Injury......…………………. • Hematuria………………………………... • Proteinuria.................................................. Acid-Base: • Anion Gap Metabolic Acidosis…..……... • Non-anion Gap Metabolic Acidosis…….. • Metabolic Alkalosis……………...……… Electrolytes: • Hyponatremia……………………………. • Hypernatremia………………………….... • Hypokalemia……………………………... • Hyperkalemia…………………………….. • Hypocalcemia……………………………. • Hypercalcemia………………………...…. • Hypo/Hypermagnesemia………..…...…... • Hypo/Hyperphosphatemia…………...…... Overview of Topics Chapter 3 Nephrology
  • 33. Pre-RenalPre-Renal Hypovolemia • GI loss • Hemorrhage Decrease in effective circulating fluid volume (ECFV) • Congestive Heart Failure • Sepsis • Shock Renal Artery Pathology • Renal Artery Obstruction: • Stenosis • Thrombosis • Dissection • Abdominal Compartment Syndrome • Renal Artery Vasoconstriction: • NSAIDs • ACE inhibitors • Angiotensin II Receptor Blockers • Hypercalcemia • Other:: • Hepatorenal syndrome Note that abdominal compartment syndrome is usually caused by large-volume ascites compressing blood flow to kidneys, and hence a pre-renal etiology to AKI. Note that abdominal compartment syndrome is usually caused by large-volume ascites compressing blood flow to kidneys, and hence a pre-renal etiology to AKI. 32 Nephrology ____________________________________________________________________________________________________________________________________________ Acute Kidney Injury (Acute Renal Failure) ____________________________________________________________________________________________________________________________________________ Definitions • Acute kidney injury and acute renal failure are synonyms used to describe an acute problem in normal kidney function, although acute kidney injury (AKI) is considered to be the better term. • The approach to acute renal failure is the same as the approach to decreased urine output, or an elevated serum creatinine. They all describe an underly- ing problem with kidney function. • A modern definition of AKI by the Acute Kidney Injury Network (AKIN) defines AKI as an abrupt (within 48 hours) absolute increase in the serum creatinine with one of the following: • A percentage increase in the serum creatinine of ≥ 50% • Serum creatine increase of ≥ 26.4 mmol/L from baseline • Urine output of < 0.5 mL/kg per hour for more than six hours _____________________ Approach: • The approach to AKI involves 3 categories: 1. Pre-Renal 2. Renal 3. Post-Renal
  • 34. 33 Nephrology ____________________________________________________________________________________________________________________________________________ Acute Kidney Injury (continued...) ____________________________________________________________________________________________________________________________________________ The short list - AKI • Pre-Renal • Hypovolemia • CHF • Sepsis/Shock • Renal • ATN • Post-Renal • BPH • Blocked foley RenalRenalRenal Vascular Microangiopathic Hemolytic Anemias (MAHA) • HUS • TTP • DIC Glomerular Glomerulonephritis • Nephrotic • Nephritic Tubulointerstitial Acute Tubular Necrosis (ATN) ______________ Acute Interstitial Nephritis (AIN) Any pre-renal cause Exogenous nephrotoxins • Aminoglycosides • IV Contrast • Chemotherapy Endogenous nephrotoxins • Myoglobin (Rhabdomylosis) • Uric Acid (Tumor Lysis) • Bence Jones protein (Myeloma) ___________________________ Drugs • Antibiotics – Penicillins, Ciprofloxacin • Sulfas – Septra, Lasix, HCTZ • NSAIDs • PPIs • Allopurinol Infiltrative • SLE, Sjogren’s, Sarcoidosis Infectious • Pyelonephritis Post-RenalPost-Renal Anatomic Obstruction • Bilateral Ureteral Obstruction: o Stones o Stricture o Tumor • Bladder Outlet Obstruction o Benign Prostatic Hypertrophy (BPH) o Prostate Cancer o Blocked Foley Catheter o Neurogenic Bladder o Anticholinergic meds
  • 35. ___________________________________________________________________ Acute Kidney Injury (continued...) ___________________________________________________________________ ___________________________________________________________________ Hematuria ___________________________________________________________________ 34 Nephrology AKI Lab Workup • Urinanalysis (U/A) • Fractional excretion of sodium (FE Na) • Urine eosinophils (if warranted) • Renal ultrasound (if warranted, to rule out obstruction) • Renal biopsy (if suspecting GN) Urinalysis findings Pre-renal • Often bland, can have Hyaline casts • FENA <1% • Note that CKD patients with pre-renal AKI can have an FENA >1% due to their decreased capacity for tubular sodium reabsorption Renal GN: • RBC casts • Dysmorphic RBCs ATN: • Granular casts (muddy brown casts) • Mild proteinuria and/or hematuria (RBCs) • FENA >2% AIN • Positive eosinophils • WBC casts (if pyelonephritis) Post-renal • Often bland • Can have hematuria DDx of HematuriaDDx of Hematuria Extra-renal (more common) Infection: • Cystitis • Urethritis • Prostatitis Neoplasm: • Prostate cancer • Bladder cancer (transitional cell cancer) Other: • Foley trauma • Nephrolithiasis Intra-renal • Nephrolithiasis • Renal cell carcinoma • Renal infarcts • Renal vein thrombosis • Trauma • Glomerulonephritis • Polycystic kidney disease Note that common systemic causes of GN that can cause hematuria to be kept in mind at the very least are SLE, Vasculitis, Endocarditis, HIV/Hep B/Hep C. Note that common systemic causes of GN that can cause hematuria to be kept in mind at the very least are SLE, Vasculitis, Endocarditis, HIV/Hep B/Hep C.
  • 36. DDx of ProteinuriaDDx of Proteinuria Glomerular • Glomerulonephritis Tubulointerstitial • ATN • AIN Hemodynamic • Hypertension (Hypertensive nephrosclerosis) • Hypertensive emergency • Congestive heart failure Overproduction of LMW proteins • Multiple Myeloma • Waldenstrom's Macroglobulinemia Hereditary • Alport's syndrome • Fabry's disease • Polycystic Kidney disease Other • Heavy Exercise • Fever • Infection • Orthostatic proteinuria Note that common systemic causes of GN that can cause proteinuria to be kept in mind are Diabetes, SLE, Amyloid/Multiple Myeloma. Note that common systemic causes of GN that can cause proteinuria to be kept in mind are Diabetes, SLE, Amyloid/Multiple Myeloma. 35 Nephrology Proteinuria Lab Workup • Urine dipstick: o Fast & cheap, but inaccurate in terms of quantification o Dipstick only becomes positive after 300 mg of protein is present within the urine, therefore it will not detect microalbuminemia o Dipstick only detects negatively charged proteins (ie. albumin), hence will not detect paraproteins involved in plasma cell dyscra- sias such as multiple myeloma necessarily. • Urine Albumin to Creatinine Ratio (ACR) versus 24 hour urine protein col- lection. Urine ACR is obviously easier for patients since it does not in- volve 24 hour urine collection. Diagnostic Hints: Diagnostic Approach to ProteinuriaDiagnostic Approach to Proteinuria If proteinuria < 1.5g per day, then likely etiologies are: Functional • Fever • Infection • Exercise • Orthostatic Overflow • Multiple Myeloma • Waldenstrom’s If proteinuria >1.5g per day, then likely etiologies are: • Glomerulonephritis • ATN • AIN ____________________________________________________________________________________________________________________________________________ Proteinuria ____________________________________________________________________________________________________________________________________________
  • 37. DDx of Anion Gap Metabolic AcidosisDDx of Anion Gap Metabolic Acidosis Ketoacidosis • Diabetic ketoacidosis (DKA) • Alcoholism • Starvation Lactic Acidosis • Type A = impairment in tissue oxygenation o Shock (4 subtypes) o Respiratory distress o Sepsis o Ischemic Bowel • Type B = no impairment in tissue oxygenation o Meds: Metformin, ASA, NRTI o Alcoholism o Malignancy Renal Failure • Any cause of Renal Failure (Acute and/or Chronic) Drugs • Salicylates • Acetaminophen • Methanol • Ethylene Glycol • Paraldehyde • Cyanide 36 Nephrology Approach to Metabolic Acidosis Definition: • Acidosis = pH <7.4 (some sources indicate pH<7.35) • Metabolic acidosis = Gain of Hydrogen or loss of Bicarbonate Diagnosis: Step 1: • Look at electrolyte panel for a low bicarbonate. • If bicarbonate low, suspect metabolic acidosis Step 2: • Perform an arterial blood gas (ABG) to look for acidosis (pH <7.4) • If acidosis is present, with a low bicarbonate, it will confirm pres- ence of underlying metabolic acidosis Step 3: • Calculate the Anion Gap (AG) = Na+ - (Cl- + HCO3-) • An elevated AG is defined as >12 (if albumin normal) • For every 10 unit decrease in albumin, add 3 units to the AG to get an AG corrected for low albumin Step 4: • Calculate compensation – 1:1 bicarbonate to CO2 • In other words, for every decrease in 1 unit for bicarbonate, the CO2 also should decrease by 1 to compensate ____________________________________________________________________________________________________________________________________________ Anion Gap Metabolic Acidosis (AGMA) ____________________________________________________________________________________________________________________________________________
  • 38. 37 Nephrology Approach to Metabolic Acidosis (continued) Step 5: • Measure the delta-delta Delta-Delta Delta-Delta = delta AG/ delta HCO3- = (expected AG - calculated AG)/ (24 – HCO3-) = (12 - calculated AG) / (24 – HCO3-) • The delta-delta is only useful in Anion Gap Metabolic Acidosis to see if there are multiple acid-base disturbances present on top of An- ion Gap Metabolic Acidosis • This is particularly useful if the compensation does not add up 1:1 Delta-Delta Significance 1-2 <1 >2 AG met acidosis AG met acidosis + non-AG met acidosis AG met acidosis + met alkalosis AGMA Lab Workup: • Creatinine & BUN • Lactate • Ketones: o Plasma beta-hydroxybutyrate o Urine dipstick acetoacetate • Serum Toxin Screen: o Salicylates o Acetaminophen o Ethanol • Serum osmolality: o Calculate osmolal gap if suspecting an underlying toxic ingestion o An elevated osmolal gap suggests the presence of an unmeasured osmole o Causes of an elevated osmolal gap (>10) are: DDx for Elevated Osmolal Gap • Methanol • Ethylene glycol • Ethanol • Isopropyl alcohol Ethanol and isopropyl alcohol do not cause an AGMA ____________________________________________________________________________________________________________________________________________ Anion Gap Metabolic Acidosis (continued...) ____________________________________________________________________________________________________________________________________________
  • 39. 38 Nephrology Osmolal Gap (OG) • OG = measured serum osmolality − calculated osmolality • Calculated osmolality = 2 x [Na mmol/L] + [glucose mmol/L] + [urea mmol/L] • It the difference between the two osmlalities is >10 (or >12 according to some sources), then it suggests that there is an underlying toxic ingestion • As the toxin is metabolized, the osmolal gap corrects back to normal quicker than the anion gap, so you may have a high AG but normal OG. Don’t be fooled. • Note: a mnemonic to remember the calculated osmolality formula of 2Na + glucose + BUN is “2 salty, sticky, buns” ____________________________________________________________________________________________________________________________________________ Anion Gap Metabolic Acidosis (continued...) ____________________________________________________________________________________________________________________________________________
  • 40. DDx of Non-Anion Gap Metabolic AcidosisDDx of Non-Anion Gap Metabolic Acidosis Positive Urine Anion Gap • Early Renal Failure • RTA type I • RTA type IV Negative Urine Anion Gap • RTA type II • Diarrhea (GI loss of HCO3-) • Rapid infusion of bicarbonate-free IV fluids (dilutional) • Drugs: o Sevelamer o Cholestyramine o Acetazolamide o Toluene 39 Nephrology Urine Anion Gap (UAG) Calculation Urine Anion Gap = (Urine Na + Urine K) – Urine Cl Note: UAG interpretation assumes that the patient is not hypovolemic and has no AG metabolic acidosis. Renal Tubular Acidosis (RTA) Details: RTA Type I RTA Type II RTA Type IV Site Distal Proximal Distal Primary defect Defective distal H+ secretion Decreased proximal reabsorption of HCO3- Hypoaldosteronism Plasma bicarbonate Variable, may be below 10 meq/L 12 to 20 meq/L > 17 meq/L Plasma Potassium Hypokalemia largely corrects with alkali therapy Hypokalemia made worse by bicarbonaturia induced by alkali therapy Hyperkalemia ____________________________________________________________________________________________________________________________________________ Non-Anion Gap Metabolic Acidosis (NAGMA) ____________________________________________________________________________________________________________________________________________
  • 41. ___________________________________________________________________ Metabolic Alkalosis ___________________________________________________________________ DDx of Metabolic AlkalosisDDx of Metabolic Alkalosis Gastrointestinal H+ loss • Vomiting • NG suction • Antacids in Chronic Kidney Disease Renal H+ loss • Diuretics (loop or thiazide) • Hypercalcemia • Hyperaldosteronism • Post-hypercapnic alkalosis Intracellular H+ shift • Hypokalemia Contraction alkalosis Any cause of hypovolemia, particularly: • GI loss • Diuresis ______________________________________________________________________________ Hyponatremia _____________________________________________________________________________ 40 Nephrology Overview: • Hyponatremia is not a deficit in sodium, but in fact relates to serum tonicity and volume status. • There are 2 parts to the differential diagnosis of hyponatremia: firstly one is based on the serum tonicity, and then the second part is a specific differen- tial diagnosis for hypotonic hyponatremia, which is the most common etiol- ogy for hyponatremia. DDx of HyponatremiaDDx of Hyponatremia Hypotonic Hypotonic hyponatremia is the most common cause of hyponatremia. See next page for the differential diagnosis of hypotonic hyponatremia. Isotonic Lab artifact from: • Hyperlipidemia • Hyperproteinemia Hypertonic Excess of an osmole that draws water intravascularly, particularly: • Hyperglycemia • Mannitol Note that every increase in glucose by 10 mmol/L causes a decrease in sodium by 3 mEq/L Note that every increase in glucose by 10 mmol/L causes a decrease in sodium by 3 mEq/L
  • 42. 41 Nephrology DDx of Hypotonic HyponatremiaDDx of Hypotonic Hyponatremia Hypervolemic • Congestive heart failure • Cirrhosis • Nephrotic syndrome • Advanced renal failure DDx of Hypotonic HyponatremiaDDx of Hypotonic Hyponatremia Hypovolemic Renal losses: • Diuretics • Hypoaldosteronism Extrarenal losses: • Vomiting • Diarrhea • Pancreatitis • Inadequate intake Euvolemic SIADH: • Any intracranial/CNS disorder • Any pulmonary disease • Drugs o Antidepressants o Antipsychotics o Carbamazepine • Miscellaneous o Pain o Nausea o Postoperative state Endocrine disorders o Hypothyroidism o Adrenal insufficiency Suppressed ADH: • Low solute diet/malnutrition • Psychogenic polydipsia • Pregnancy ____________________________________________________________________________________________________________________________________________ Hyponatremia (continued...) ____________________________________________________________________________________________________________________________________________ The Short List - Hyponatremia 1. Hypovolemia 2. SIADH 3. Hypothyroidism 4. Adrenal insufficiency 5. Low solute diet 6. Hypervolemia
  • 43. 42 Nephrology Approach Step 1: Determine if the patient is symptomatic: • Severe Symptoms: seizure, lethargy, stupor, coma. If so, this is a medical emergency should be treated immediately (see manage- ment) • Absence of Severe Symptoms: continue to Step 2 Step 2: Determine the serum osmolality: • HyperOSM (>300 mOsm/kg): Hyperglycemia (ie. DKA or HHS) - correct by adding 3mmol/L of Na for every 10mmol/L ↑ in glucose • IsoOSM (275-300 mOsm/kg): severe paraproteinemia (myeloma) or hypertriglyceridemia • HypoOSM (<275 mOsm/kg): continue to Step 3 Step 3: Determine the urine osmolality: • Low (<100 mOSM/kg): due to psychogenic polydipsia or de- creased solute intake (beer potomania, tea and toasters) • Non-Low (>100 mOSM/kg): Continue to step 4 Approach (...) Step 4. Determine the patient’s volume status: • Hypervolemic - CHF, Cirrhosis, Nephrotic syndrome • Hypovolemic - renal vs extrarenal losses of fluid • Euvolemic – SIADH vs other Step 5. Treat the underlying cause SIADH Findings • Euvolemic • Urine osmolality at least >100, usually >300 • Urine sodium >40 ____________________________________________________________________________________________________________________________________________ Hyponatremia (continued...) ____________________________________________________________________________________________________________________________________________
  • 44. ___________________________________________________________________ Hypernatremia ___________________________________________________________________ DDx of HypernatremiaDDx of Hypernatremia Extra-renal Water Loss • Vomiting • NGT • Diarrhea • Insensible losses (fever, exercise) Renal Water Loss • Diuretics • Diabetes insidipus: Central: o Tumor o Trauma o Infiltrative disease o Hypoxic encephalopathy Nephrogenic: o Lithium o Hypercalcemia o Recovery phase of ATN o Post-obstruction Other • Hypertonic saline administration • Hyperaldosteronism • Seizures ___________________________________________________________________ Hypokalemia ___________________________________________________________________ DDx of HypokalemiaDDx of Hypokalemia Increased entry into cells • Insulin • Beta agonists • Alkalosis • Hypothermia Increased GI loss • Diarrhea Note: Vomiting and NG tube drainage cause hypokalemia but manifest as renal losses due to metabolic alkalosis and secondary hyperaldosteronism Increased Renal loss • Diuretics • Hypomagnesemia • Renal Tubular Acidosis (RTA) types I and II • Hyperaldosteronism • Bartter’s & Gitelman’s syndromes Other • Dialysis • Plasmapheresis 43 Nephrology Note: Hypernatremia is a deficit of water relative to sodium. It is usually from a loss of hypotonic fluid and impaired access to free water. Therefore, all pa- tients with hypernatremia are hypertonic. Hypokalemia On ECGHypokalemia On ECG Hypokalemia - Prolonged, flat T waves - U waves - ST depression
  • 45. DDx of Hypokalemia associated with Acid-Base Abnormalities: Hypokalemia and Acid-Base AbnormalitiesHypokalemia and Acid-Base Abnormalities Hypokalemia and metabolic acidosis (NAGMA) • RTA type I • RTA type II Hypokalemia and metabolic alkalosis Low urine chloride (<20): • Vomiting • NG tube drainage • Diuretics High urine chloride (>40): • Hyperaldosteronism • Bartter’s & Gitelman’s syndromes 44 Nephrology Notes on Hypokalemia • Oral replacement with Potassium Chloride (KCl) is preferable over intra- venous KCL since potassium can be more rapidly repleted orally. • Oral KCl can be given either in solid (K-Dur) or liquid format (K- Elixir). The K-Dur is a large pill that is sometimes difficult to swallow for patients, while the K-Elixir tastes awful according to many patients. There is otherwise no noted difference in effectiveness between the two. • Patients with hypomagnesemia often need magnesium supplementation in addition to potassium supplementation in order to correct their hypo- kalemia. ____________________________________________________________________________________________________________________________________________ Hypokalemia (continued...) ____________________________________________________________________________________________________________________________________________
  • 46. DDx of HyperkalemiaDDx of Hyperkalemia Increased release from cells Cell lysis • Hemolysis • Rhabdomyolysis • Tumor lysis syndrome Cell release: • Digoxin overdose • Beta blockers • Metabolic acidosis • Hyperglycemia/Insulin deficiency (ie. DKA) Decreased urinary excretion • Renal failure (Acute or Chronic) • Hypoaldosteronism/RTA type 4 45 Nephrology Hyperkalemia on ECG On ECGOn ECG Hyperkalemia In chronological order based on severity: 1. Tall, Peaked T waves (usually 1st change seen) 2. Increased PR interval 3. Wide QRS 4. Loss of P wave 5. Sine wave (severe, late change) ____________________________________________________________________________________________________________________________________________ Hyperkalemia ____________________________________________________________________________________________________________________________________________
  • 47. DDx of HypocalcemiaDDx of Hypocalcemia Pseudo- hypoparathyroidism (high PTH) • PTH end organ resistance Hypoparathyroidism (low PTH) • Hypomagnesemia • Thyroidectomy • Parathyroidectomy • Radiation induced destruction of parathyroids • Infiltration of parathyroid (ie. hemochromatosis) Vit D deficiency • Low sunlight exposure • Gut Malabsorption (IBD, Celiac, etc) • Drugs (anticonvulsants, ketoconazole) CKD • CKD (secondary hyperparathyroidism) Calcium sequestration • Pancreatitis • Hyperphosphatemia (AKI, Rhabdo, Tumor lysis) • Blood transfusions (citrate binding to calcium) 46 Nephrology Hypocalcemia on ECG On ECGOn ECG Hypocalcemia Prolonged QT segment Hypocalcemia Treatment • Calcium supplementation o IV Calcium gluconate or Calcium chloride in severe hypocalcemia or in symptomatic patients o PO Calicum carbonate in asymptomatic patients • Magnesium sulfate (MgSO4) o If Magnesium levels are low, do not forget to replete as well to en- sure that Calcium is well absorbed o Usually recommended to repeat dosing 2 to 3 times, several hours apart, to ensure correction since magnesium sulfate is not readily absorbed • Vitamin D (Ergocalciferol or Cholecalciferol) o Administer in vitamin D deficiency ____________________________________________________________________________________________________________________________________________ Hypocalcemia ____________________________________________________________________________________________________________________________________________
  • 48. 47 Nephrology Hints & Tips • Before establishing a diagnosis of hypercalcemia, serum calcium needs to be corrected for albumin level. This means, for every 10 unit decrease in the albumin, you must add 0.2 units to the serum calcium to have a cor- rected level • Alternatively you can order a serum ionized calcium level, which will give you the actual serum calcium regardless of albumin levels • Primary hyperparathyroidism and malignancy account for the majority of cases of hypercalcemia • The presence of longstanding asymptomatic hypercalcemia is more sug- gestive of primary hyperparathyroidism • Primary hyperparathyroidism is often associated with mild hypercalce- mia, with serum levels often <2.75 mmol/L. Serum calcium values >3.25 mmol/L are unusual in primary hyperparathyroidism and are more com- mon in malignancy On ECG: On ECGOn ECG Hypercalcemia • Shortened QT segment ____________________________________________________________________________________________________________________________________________ Hypercalcemia ____________________________________________________________________________________________________________________________________________ DDx of HypercalcemiaDDx of Hypercalcemia PTH-mediated (High PTH) • Primary Hyperparathyroidism • Tertiary hyperparathyroidism (chronic kidney disease) • Familial hypocalciuric hypercalcemia (FHH) • Lithium PTH-independent (low PTH) Malignancy: • Leukemia, Lymphoma, Multiple Myeloma • Humoral (PTH-related protein): o Squamous cell carcinomas (lung/esophagus) o Breast/Renal/Bladder/Ovarian carcinoma • Bone metastases: o Breast/Lung/Thyroid/Kidney/Prostate cancers Endocrine: • Hyperthyroidism • Adrenal insufficiency Drugs: • Thiazides (ie. HCTZ) • Vitamin D intoxication • Vitamin A intoxication • Excessive Calcium Carbonate Granulomatous disorders (cause 1-25-Vit D excess): • Tuberculosis • Sarcoidosis • Wegener’s granulomatosis Other: • Immobilization
  • 49. 48 Nephrology Hypercalcemia - Workup • The first step in the investigation of hypercalcemia is to get a PTH level, in addition to Calcium and Phosphate levels. • An elevated PTH value or a PTH value in the upper half of the normal range in the setting of hypercalcemia is likely the result of primary hy- perparathyroidism. • PTH concentrations that are normal or low indicate the need for evalua- tion of causes other than primary hyperparathyroidism as the etiology for the hypercalcemia. Theses tests include: o 24 hour urinary calcium excretion o Urine calcium to creatinine clearance ratio (Ca/Cr clearance) (also known as urine fractional excretion of calcium (FE Ca)) o PTH related peptide (PTHrp) o SPEP & UPEP o TSH o 1,25-dihydroxyvitamin D (calcitriol) o 25-hydroxyvitamin D (calcidiol) o Vitamin A • The urine calcium to creatinine clearance ratio is measured from a fast- ing morning spot urine collection. The formula for determining the cal- cium to creatinine clearance ratio is (urine calcium × serum creatinine)/ (serum calcium × urine creatinine) • Note that elevated levels of calcitriol are suggestive of underlying lym- phoma or granulomatous disorders, whil elevated calcidiol levels are indicative of vitamin D intoxication ____________________________________________________________________________________________________________________________________________ Hypercalcemia (continued) ____________________________________________________________________________________________________________________________________________
  • 50. ___________________________________________________________________ Hypomagnesemia ___________________________________________________________________ DDx of HypomagnesemiaDDx of Hypomagnesemia GI loss • Vomiting • Diarrhea • NG suction • Pancreatitis (saponification of Mg in necrotic fat) Renal loss Drugs: • Diuretics (loops and thiazides) • Alcohol • Aminoglycosides Other: • Hypercalcemia (Ca & Mg compete for transport in the Loop of Henle) • Hyperaldosteronism • Primary renal wasting (hereditary, diagnosis of exclusion) ___________________________________________________________________ Hypermagnesemia ___________________________________________________________________ DDx of HypermagnesemiaDDx of Hypermagnesemia Decreased loss • Renal failure Increased intake • Oral ingestion • IV infusion Other • Diabetic ketoacidosis • Tumor lysis syndrome • Adrenal insufficiency • Lithium 49 Nephrology
  • 51. ___________________________________________________________________ Hypophosphatemia ___________________________________________________________________ DDx of HypophosphatemiaDDx of Hypophosphatemia Redistribution (Intracellular shift) • Insulin • Acute respiratory alkalosis • Hungry bone syndrome Decreased intestinal absorption • Inadequate intake • Chronic diarrhea • Vitamin D deficiency • Antacids Increased urinary excretion • Hyperparathyroidism • Acute volume expansion • Osmotic diuresis 
 ___________________________________________________________________ Hyperphosphatemia ___________________________________________________________________ DDx of HyperphosphatemiaDDx of Hyperphosphatemia Intracellular release • Tumor lysis syndrome • Rhabdomyolysis • Lactic acidosis • Ketoacidosis Increased renal reabsorption • Hypoparathyroidism • Acromegaly • Bisphosphonates Decreased renal loss • Renal failure Pseudohyperphosphatemia • Hyperglobulinemia (Multiple myeloma) • Hyperlipidemia • Hyperbilirubinemia 50 Nephrology
  • 52. On history: • Oropharyngeal Dysphagia……………… • Esophageal Dysphagia…………….... • Abdominal Pain………………………......... • Upper GI Bleed…………………………...... • Lower GI Bleed…………………………..... • Diarrhea…………………………………........ • Bloody Diarrhea…………………………... • Constipation……………………………….... On physical: • Hepatomegaly………………………….….   • Splenomegaly……………………............. • Ascites…………………………………........ On labs: • Elevated Transaminases……………………... • Elevated Biliary Tract Enzymes …………..   • Conjugated Hyperbilirubinemia………….… • Unconjugated Hyperbilinemia……………... • Hypoalbuminemia…………………………....... • Elevated amylase…………………….…. • Elevated lipase…………………….……. Chapter 4 Gastro- enterology Overview of Topics
  • 53. ___________________________________________________________________ Oropharyngeal Dysphagia ___________________________________________________________________ DDx of Oropharyngeal DysphagiaDDx of Oropharyngeal Dysphagia Neurological • Stroke • Parkinson’s disease • Bell’s palsy Neuromuscular • Myasthenia gravis • Multiple sclerosis • Amyotrophic lateral sclerosis (ALS) • Polymositis • Muscular dystrophy Other • Zencker’s Diverticulum • Pharyngitis • Enlarged thyroid • Neck mass ___________________________________________________________________ Esophageal Dysphagia ___________________________________________________________________ DDx of DysphagiaDDx of Dysphagia Solids Only (Mechanical Obstruction) • Intermittent: o Esophageal rings (in lower esophagus) o Esophageal webs (in upper esophagus) • Progressive: o Peptic stricture o Esophageal cancer Solids and/or Liquids (Motility Disorder) • Intermittent: o Diffuse esophageal spasm (DES) o Non-specific esophageal motility disorder (NEMD – dx of exclusion) • Progressive: o Achalasia o Scleroderma 52 Gastroenterology Notes • Oropharyngeal dysphagia is defined as a difficulty in initiating swallow- ing. It can be often associated with coughing, choking, and/or nasal re- gurgitation of food. • Oropharyngeal dysphagia is caused by underlying neurologic or muscu- lar disease. Notes • Esophageal dysphagia is defined as a sensation of food getting stuck or lodged in the esophagus. • Esophageal dysphagia of solids only is due to an underlying mechanical obstruction, whereas in esophageal dysphagia with both solids and liq- uids, there is an underlying motility disorder. • Note that achalasia is the most common etiology among the motility disor- ders causing esophageal dysphagia On history
  • 54. DDx of Abdominal PainDDx of Abdominal Pain Epigastric • Pancreatitis • GERD • Peptic Ulcer Disease • Gastritis • Gastroenteritis • Myocardial Infarct • Ruptured Aortic Aneurysm Periumbilical • Early Appendicitis • Ruptured Aortic Aneurysm • Gastroenteritis • Bowel obstruction Diffuse Abdominal: • Gastroenteritis • Bowel ischemia • Peritonitis • Irritable Bowel Syndrome Other: • Diabetic ketoacidosis • Porphyria • Malaria • Familial Mediterranean fever 53 Gastroenterology DDx of Abdominal PainDDx of Abdominal Pain Right Upper Quadrant • Hepatitis • Cholecystitis • Cholangitis • Budd-Chiari syndrome • Pneumonia/Empyema/Pleurisy • Sub-diaphragmatic abscess Left Upper Quadrant • Gastritis • Gastric Ulcer • Splenic Infarct • Splenic Abscess Right Lower Quadrant • Appendicitis • Inflammatory Bowel Disease • Nephrolithiasis • Inguinal Hernia • Pelvic Inflammatory Disease • Ectopic pregnancy Left Lower Quadrant • Diverticulitis • Inflammatory Bowel Disease • Nephrolithiasis • Inguinal Hernia • Pelvic Inflammatory Disease • Ectopic pregnancy ____________________________________________________________________________________________________________________________________________ Abdominal Pain ____________________________________________________________________________________________________________________________________________ On history
  • 55. ___________________________________________________________________ Upper GI Bleed (UGIB) ___________________________________________________________________ DDx of UGIBDDx of UGIB Ulcerative/Erosive • Peptic Ulcer Disease • Esophagitis Portal Hypertension • Esophageal Varices • Gastric Varices • Duodenal Varices Traumatic • Mallory-Weiss tear Neoplastic • Benign tumor • Adenocarcinoma • Kaposi’s sarcoma Vascular • Angiodysplasia • Osler-Weber-Rendu syndrome ___________________________________________________________________ Lower GI Bleed (LGIB) ___________________________________________________________________ DDx of LGIBDDx of LGIB Anatomical • Diverticulosis Vascular • Angiodysplasia • Ischemic colitis/Mesenteric ischemia • Radiation-induced telangiectasia Inflammatory • Infectious colitis • Inflammatory Bowel Disease Neoplastic • Polyp • Carcinoma Other • Hemorrhoid • Anal Fissure • Ulcer 54 Gastroenterology On history
  • 56. DDx of Bloody DiarrheaDDx of Bloody Diarrhea Infectious Bacterial: • E. coli (2 types): o Entero-invasive o 0157:H7 • Salmonella • Shigella • Campylobacter • Yersinia enterocolitica • Vibrio (less likely) • C. difficile (if toxic megacolon) Viral: • CMV colitis (in immunosuppressed) Parasitic: • Entamoeba histolytica Inflammatory • Inflammatory bowel disease (IBD) • Bowel ischemia • Diverticulosis • Radiation enteritis Neoplastic • Colon cancer • Lymphoma 55 Gastroenterology On history ____________________________________________________________________________________________________________________________________________ Bloody Diarrhea ____________________________________________________________________________________________________________________________________________ The Short List - Bloody Diarrhea 1. Bacterial 2. Viral 3. Parasitic 4. IBD 5. Diverticulosis 6. Colon cancer
  • 57. DDx of Non-Bloody DiarrheaDDx of Non-Bloody Diarrhea Infectious Bacteria: • C. difficile • Staph aureus • Clostridium perfringens • Bacillus cereus • Vibrio cholera & parahaemolyticus • Mycobacterium avium (in immunosuppressed) Viruses: • Rotavirus • Norovirus • Adenovirus • CMV (in immunosuppressed) Other: • Giardia • Note: all infectious causes of bloody diarrhea can also potentially present as non-bloody diarrhea • Note: all infectious causes of bloody diarrhea can also potentially present as non-bloody diarrhea Inflammatory • Inflammatory bowel disease (Crohn’s > UC) • Bowel ischemia • Diverticulitis • Radiation enteritis Neoplastic • Colon cancer • Lymphoma within the GI tract DDx of Non-Bloody DiarrheaDDx of Non-Bloody DiarrheaDDx of Non-Bloody Diarrhea Malabsorption Bile salt deficiency: • Cirrhosis Pancreatic insufficiency: • Chronic pancreatitis Mucosal abnormalities: • Bacterial overgrowth • Lactose intolerance • Celiac disease • Tropical sprue • Whipple’s disease Bile salt deficiency: • Cirrhosis Pancreatic insufficiency: • Chronic pancreatitis Mucosal abnormalities: • Bacterial overgrowth • Lactose intolerance • Celiac disease • Tropical sprue • Whipple’s disease Secretory • Gastrinoma (Zollinger-Ellison syndrome) • VIPoma • Carcinoid tumor • Laxative abuse • Gastrinoma (Zollinger-Ellison syndrome) • VIPoma • Carcinoid tumor • Laxative abuse Motility • Irritable bowel syndrome • Scleroderma • Diabetic autonomic neuropathy (or dysmotility) • Irritable bowel syndrome • Scleroderma • Diabetic autonomic neuropathy (or dysmotility) • Hyperthyroidism, although commonly included in the ddx for diarrhea, in fact does not truly present with diarrhea but instead with an increased incidence of bowel movements • Hyperthyroidism, although commonly included in the ddx for diarrhea, in fact does not truly present with diarrhea but instead with an increased incidence of bowel movements • Hyperthyroidism, although commonly included in the ddx for diarrhea, in fact does not truly present with diarrhea but instead with an increased incidence of bowel movements 56 Gastroenterology On history ____________________________________________________________________________________________________________________________________________ Non-Bloody Diarrhea ____________________________________________________________________________________________________________________________________________
  • 58. ___________________________________________________________________ Chronic Diarrhea ___________________________________________________________________ DDx of Chronic DiarrheaDDx of Chronic Diarrhea Infectious • HIV and related infections Inflammatory • Inflammatory bowel disease • Microscopic colitis • Radiation enteritis Malabsorption Bile salt deficiency: • Cirrhosis Pancreatic insufficiency: • Chronic pancreatitis Mucosal abnormalities: • Bacterial overgrowth • Lactose intolerance • Celiac disease, Tropical sprue, Whipple’s disease Secretory • Gastrinoma (Zollinger-Ellison syndrome) • VIPoma • Carcinoid tumor • Laxative abuse • Short bowel syndrome • Post-cholecystectomy • Bile acids are re-absorbed in the terminal ileum. In patients with no terminal ileum (ie. short bowel syndrome), excessive amounts of bile acids enter the colon and cause diarrhea. Similar principle applies post- cholecystectomy. • Bile acids are re-absorbed in the terminal ileum. In patients with no terminal ileum (ie. short bowel syndrome), excessive amounts of bile acids enter the colon and cause diarrhea. Similar principle applies post- cholecystectomy. ___________________________________________________________________ Constipation ___________________________________________________________________ DDx of ConstipationDDx of Constipation Obstruction • Cancer • Stricture Endocrine • Diabetes mellitus • Hypothyroidism • Panhypopituitarism • Pregnancy Metabolic • Hypokalemia • Hypercalcemia Drugs • Opiates • Antidepressants • Antipsychotics • Antihistamines • Iron supplements Neurogenic • Parkinson’s disease • Multiple sclerosis • Spinal cord injury 57 Gastroenterology On history
  • 59. DDx of HepatomegalyDDx of Hepatomegaly Cirrhotic • Any cause of cirrhosis Neoplastic • Hepatocellular carcinoma • Leukemia • Lymphoma • Multiple Myeloma Infectious • Infectious Mononucleosis • Hepatitis • Liver abscess • Malaria Metabolic • Amyloidosis • Fatty liver disease (steatohepatitis) Drugs • Alcohol Cardiac • Right heart failure 58 Gastroenterology On physical The Short List - Hepatomegaly 1. Cirrhosis 2. Leukemia/Lymphoma 3. Infectious Mononucleosis 4. Fatty liver disease 5. Right heart failure ____________________________________________________________________________________________________________________________________________ Hepatomegaly ____________________________________________________________________________________________________________________________________________
  • 60. DDx of SplenomegalyDDx of Splenomegaly Hematologic/ Neoplastic • Leukemia • Lymphoma • Multiple myeloma • Myelofibrosis • Polycythemia vera • Essential thrombocytosis • Sickle cell disease • Metastatic solid tumors Infectious Viral: • EBV (infectious mononucleosis) • CMV • HIV Bacterial: • Endocarditis • Tuberculosis Parasitic: • Malaria • Schistosomiasis Congestive • Right Heart failure • Cirrhosis • Thrombosis of portal, hepatic, or splenic veins Inflammatory • Sarcoidosis • Systemic lupus erythematosus (SLE) • Rheumatoid arthritis 59 Gastroenterology The Short List - Splenomegaly 1. Leukemia 2. Lymphoma 3. Metastatic solid tumor 4. Infectious Mononucleosis 5. CHF 6. Cirrhosis On physical ____________________________________________________________________________________________________________________________________________ Splenomegaly ____________________________________________________________________________________________________________________________________________
  • 61. DDx of AscitesDDx of Ascites SAAG > 11 (Portal Hypertension related) Pre-Sinusoidal: • Portal vein thrombosis • Splenic vein thrombosis • Schistosomiasis Sinusoidal: • Cirrhosis • Spontaneous Bacterial Peritonitis • Acute Hepatitis • Malignancy • Hepatocellular carcinoma • Pancreatic adenocarcinoma • Metastatic disease to liver/pancreas Post-Sinusoidal: • Right sided CHF • Budd-Chiari syndrome SAAG <11 (No Portal Hypertension) Infectious: • Peritonitis • Tuberculosis • HIV • Pelvic Inflammatory Disease Other: • Peritoneal carcinomatosis • Pancreatitis • Hypoalbuminemia • Dialysis • Meig’s syndrome 60 Gastroenterology The Short List - Ascites 1. Cirrhosis 2. CHF 3. Malignancy Approach • The differential of ascites is often first based upon the Serum Album to Ascites Gradient (SAAG). SAAG = Serum Albumin – Ascites Albumin • A SAAG of greater than 11 is related to underlying portal hypertension. Think of this as being similar in underlying physiology to a transudative effusion. • A SAAG of less than 11 is not related to any underlying portal hyperten- sion. Think of this as being similar to an exudative effusion. • It is important to note malignancies that cause cirrhosis and resultant por- tal hypertension present with a SAAG >11. Malignancies such as perito- neal carcinomatosis which do not cause cirrhosis, will present with a SAAG <11. On physical/ On labs ____________________________________________________________________________________________________________________________________________ Ascites ____________________________________________________________________________________________________________________________________________
  • 62. DDx of TransaminitisDDx of Transaminitis Infectious • Hepatitis A, B, C, D, & E • HIV/CMV/EBV/HSV Drugs Most common: • Alcohol • Acetaminophen Other: • Statins • Amiodarone • Azoles (Fluconazale/Itraconazole/Voriconazole) • Antiepileptics - Phenytoin • Anti-Tuberculosis drugs - INH, Rifampin • Propylthiouracil (PTU) • Chemotherapy Metabolic • Non-alcoholic steatohepatitis (NASH) • Non-alcoholic fatty liver disease (NAFLD) Vascular • Congestive heart failure • Ischemic hepatitis (“shock liver”) • Budd-Chiari syndrome Hereditary • Hemochromatosis • Wilson’s disease • Alpha-1-antitrypsin deficiency • Celiac disease Autoimmune • Autoimmune hepatitis 61 Gastroenterology On labs ____________________________________________________________________________________________________________________________________________ Elevated Transaminases (Transaminitis/Elevated AST&ALT) ____________________________________________________________________________________________________________________________________________ Transaminitis in Pregnancy: In patients who develop transaminitis during pregnancy, the usual causes should be ruled out, in addition to looking for pregnancy specific causes, outlined below: DDx of Pregnancy-induced TransaminitsDDx of Pregnancy-induced Transaminits 1st trimester • Nausea & vomiting of pregnancy (NVP) 2nd & 3rd trimesters • Acute fatty liver of pregnancy • Cholestasis of pregnancy • Pre-eclampsia/Eclampsia • HELLP syndrome The Short List - Transaminitis 1. Infectious - Hepatitis B & C 2. Drugs - Alcohol & Tylenol 3. Vascular - CHF & Shock 4. Hereditary - Hemochromatosis 5. NAFLD
  • 63. ___________________________________________________________________ Elevated Biliary Tract Enzymes (ALK & GGT) ___________________________________________________________________ DDx of elevated ALK & GGTDDx of elevated ALK & GGT Biliary obstruction • Cholecystitis • Choledocholithiasis • Ascending cholangitis • Primary sclerosing cholangitis • Primary biliary cirrhosis • Cholangiocarcinoma • Pancreatic cancer Hepatocellular dysfunction • Hepatitis • Cirrhosis • Sepsis ___________________________________________________________________ Conjugated Hyperbilirubinemia (elevated direct bilirubin) ___________________________________________________________________ DDx of Conjugated HyperbilirubinemaDDx of Conjugated Hyperbilirubinema Extrahepatic cholestasis (biliary obstruction) • Choledocholithiasis • Cholangitis • Primary sclerosing cholangitis • Primary biliary cirrhosis • Pancreatitis • Malignancy - Pancreatic, Cholangiocarcinoma • Biliary tract strictures (trauma, post-ERCP) • Liver flukes Intrahepatic cholestasis • Most causes of transaminitis can potentially also result in conjugated hyperbiliribinemia 62 Gastroenterology The Short List 1. Choledocholithiasis 2. Cholangitis 3. Pancreatitis 4. Pancreatic cancer The Short List 1. Cirrhosis 2. Hemolysis 3. Gilbert’s On labs
  • 64. ___________________________________________________________________ Unconjugated Hyperbilirubinemia (elevated indirect bilirubin) ___________________________________________________________________ DDx of Unconjugated HyperbilirubinemaDDx of Unconjugated Hyperbilirubinema Increased bilirubin production • Hemolysis Impaired bilirubin conjugation • Cirrhosis • Crigler-Najjar syndrome • Gilbert’s syndrome • Wilson’s disease • Hyperthyroidism Impaired hepatic bilirubin uptake • Congestive heart failure ___________________________________________________________________ Hypoalbuminemia ___________________________________________________________________ DDx of HypoalbuminemiaDDx of Hypoalbuminemia Most Common • Malnutrition (decreased intake) • Cirrhosis (decreased production) • Nephrotic syndrome (increased loss) Other • Protein losing enteropathy (increased loss of albumin from increased permeability of GI tract due to mucosal disease): o Inflammatory bowel disease o Pseudomembranous colitis o Gastroenteritis o Gastritis o Celiac disease o GI malignancy o Post-chemotherapy 63 Gastroenterology Note Albumin is a negative acute phase reactant, meaning that it will be low in in- flammatory states. On labs
  • 65. ___________________________________________________________________ Elevated Amylase ___________________________________________________________________ DDx of Elevated AmylaseDDx of Elevated Amylase Pancreatic • Acute Pancreatitis • Chronic Pancreatitis • Pancreatic tumor • Trauma • Surgery • ERCP Other GI disease • Acute cholecystitis • Duodenal ulcer • Bowel obstruction • Bowel infarction • Appendicitis • Liver disease • Severe gastroenteritis • Celiac disease Neoplastic • Solid tumors of the lung, esophagus, thymus, breast, ovary, & prostate Gynecologic • Ruptured ectopic pregnancy • Pelvic inflammatory disease • Ovarian cysts • Pregnancy Other • DKA • HIV • Renal Failure • Alcoholism • Drug-induced • Idiopathic ___________________________________________________________________ Elevated Lipase ___________________________________________________________________ DDx of Elevated LipaseDDx of Elevated Lipase Pancreatic • Acute pancreatitis • Chronic pancreatitis • Pancreatic tumor Other GI disease • Acute cholecystitis • Duodenal ulcer • Bowel obstruction • Bowel infarction • Celiac disease Other • DKA • HIV • Drug-induced • Idiopathic 64 Gastroenterology On labs
  • 66. On history/physical: • Lymphadenopathy………………………... On labs: • Leukocytosis……………………………… • Lymphocytosis…………………………… • Neutropenia................................................. • Anemia……………………………………. • Hemolytic Anemia………………………… • Thrombocytopenia…………...…………… • Neutropenia………………….……………. • Pancytopenia……………………………… • Coagulopathy……………………………... • Hypercoagulability/Thrombophilia.....…… • Elevated LDH……………..……………… • Elevated D-dimer…………………………. • Iron overload……………………………… Chapter 5 Hematology Overview of Topics
  • 67. 66 Hematology DDx of LymphadenopathyDDx of Lymphadenopathy Infectious Bacterial: Localized: • Strep pharyngitis • Bartonella (cat scratch disease) • Chancroid Generalized: • Tuberculosis • Secondary syphilis • Lyme disease • Lymphogranuloma venereum Viral: • HIV • EBV • CMV • HSV • Hepatitis B • Measles/Mumps/Rubella Fungal: • Histoplasmosis • Coccidioidomycosis • Cryptococcosis Protozoal: • Toxoplasmosis • Leishmaniasis The Short List - Generalized Lymphadenopathy 1. Leukemia 2. Lymphoma 3. Metastatic solid tumor 4. Infectious Mononucleosis 5. HIV 6. Tuberculosis ____________________________________________________________________________________________________________________________________________________________________ Lymphadenopathy ____________________________________________________________________________________________________________________________________________________________________ DDx of Lymphadenopathy (continued)DDx of Lymphadenopathy (continued) Neoplastic • Lymphoma • Leukemia • Metastatic disease Rheumatologic • SLE • Rheumatoid arthritis • Sarcoidosis Drugs • Drug reactions (ie. phenytoin) • Serum sickness
  • 68. ________________________________________________________________________ Leukocytosis ________________________________________________________________________ DDx of LeukocytosisDDx of Leukocytosis Infectious • Any infection (bacterial, viral, fungal, or other) Rheumatologic • Any rheumatological disease Neoplastic • Any neoplastic condition GI • Pancreatitis • Inflammatory bowel disease • Other bowel inflammation (ie. colitis, appendicitis, diverticulitis) Drugs • Steroids Tissue necrosis • Myocardial infarction • Pulmonary infarct from embolism • Bowel ischemia • Myositis • Trauma • Burns ________________________________________________________________________ Lymphocytosis ________________________________________________________________________ DDx of LymphocytosisDDx of Lymphocytosis Neoplastic • Acute lymphoblastic leukemia (ALL) • Chronic lymphocytic leukemia (CLL) • Lymphoma • Thymoma Infectious Viral: • Infectious mononucleosis (EBV) • CMV • HIV Bacterial: • Tuberculosis • Syphilis • Toxoplasmosis Other • Rheumatoid arthritis • Hyperthyroidism • Drug-induced • Cigarette smoking • Post-splenectomy 67 Hematology The Short List - Leukocytosis 1. Infection 2. Rheumatological disorder 3. Leukemia 4. Steroids 5. Tissue necrosis
  • 69. DDx of NeutropeniaDDx of Neutropenia Infectious • Any infection Neoplastic • Leukemia • Lymphoma Drug Induced • Chemotherapy • DMARDs • Thionamides (ie. PTU) • Clozapine Nutritional • Alcoholism • Illicit drugs • Vitamin B12 deficiency • Folate deficiency Rheumatologic • SLE Other • Transfusion reaction • Hypersplenism 68 Hematology The Short List - Neutropenia 1. Chemotherapy 2. Alcoholism 3. Other drugs Definitions • Neutropenia is defined as a low absolute neutrophil count (ANC). Mild neutropenia corresponds to an ANC between 1000 and 1500/ microL, moderate between 500 and 1000/microL, and severe with less than 500/microL. The risk of infection begins to increase at an ANC below 1000/microL. • Leukopenia refers to a low total white blood cell count that may be due to any cause; however, almost all leukopenic patients are neutro- penic since the number of neutrophils is so much larger than the number of lymphocytes. • Agranulocytosis literally means the absence of granulocytes. It is often a term used synonymously with pancytopenia, although the term is also sometimes incorrectly used to indicate neutropenia (ie, ANC less than 500/microL). Noteworthy • Neutropenia is most commonly encountered in patients on chemotherapy, often at its worst around day 10 post-chemo. • It is crucial that all neutropenic patients be monitored for fever, in which case they would be diagnosed with febrile neutropenia. • Febrile neutropenia is a medical emergency that requires immediate therapy with antibiotics, whereas neutropenia alone without fever does not necessarily need to be treated with antibiotics. ____________________________________________________________________________________________________________________________________________________________________ Neutropenia ____________________________________________________________________________________________________________________________________________________________________
  • 70. DDx of AnemiaDDx of Anemia Microcytic (MCV<80) • Iron Deficiency (blood loss or dietary deficiency) • Anemia of Chronic Disease (malignancy, inflammation, infection; late in disease) • Thalassemia • Sideroblastic Anemia • Lead Poisoning Normocytic (MCV 80 – 100) • See following page Macrocytic (MCV >100) • Folate deficiency • Vitamin B12 deficiency • Alcohol abuse • Liver Disease • Reticulocytosis • Myelodysplastic syndromes (MDS) • Hypothyroidism • Multiple myeloma • Drug-induced anemia: o Hydroxyurea o Methotrexate o Azathioprine 69 Hematology The Short List - Anemia DDx of AnemiaDDx of Anemia Microcytic Anemia • Iron deficiency • Anemia of chronic disease Normocytic Anemia • Blood loss • Anemia of chronic disease • Hemolysis Macrocytic Anemia • Alcohol abuse • Liver disease Contrary to what is commonly taught in most medical schools, B12 and folate deficiency are quite rare causes of macrocytic anemia in developed nations in comparison to alcohol and liver disease which are much more common. ____________________________________________________________________________________________________________________________________________________________________ Anemia ____________________________________________________________________________________________________________________________________________________________________
  • 71. Differential Diagnosis of Normocytic AnemiaDifferential Diagnosis of Normocytic Anemia Low/Normal Reticulocytes General: • Acute blood loss • Anemia of chronic disease (seen early in disease processes where there is underlying inflammation) Bone Marrow Failure: • MDS • Aplastic Anemia Bone Marrow Infiltration: • Leukemia • Lymphoma • Multiple Myeloma • Metastatic tumor • Granulomatous disease Organ failure: • Cirrhosis • Chronic Kidney Disease • Hypothyroidism • Adrenal insufficiency DDx of Normocytic AnemiaDDx of Normocytic Anemia High Reticulocytes General: • Blood Loss Hemolysis: • Micorangiopathic Hemolytic Anemia (MAHA): o Hemolytic Uremic Syndrome (HUS) o Thrombotic Thrombocytopenic Purpura (TTP) o Disseminated Intravascular Coagulation (DIC) • Autoimmune Hemolytic Anemia • Traumatic Hemolysis Hemoglobinopathies: • Sickle cell disease Membranopathies: • Spherocytosis • Elliptocytosis Enzymopathies: • G6PD Deficiency • Pyruvate Kinase Deficiency 70 Hematology ____________________________________________________________________________________________________________________________________________________________________ Anemia (continued) ____________________________________________________________________________________________________________________________________________________________________
  • 72. DDx of HemolysisDDx of Hemolysis Intravascular RBC destruction • Micorangiopathic Hemolytic Anemia (MAHA): o Hemolytic Uremic Syndrome (HUS) o Thrombotic Thrombocytopenic Purpura (TTP) o Disseminated Intravascular Coagulation (DIC) • Autoimmune hemolytic anemia (AIHA) • Traumatic hemolysis: o Hypertensive emergency o Artificial heart valve • Transfusion reactions • Scleroderma renal crisis Intrinsic RBC defects Hemoglobinopathies: • Sickle cell disease • Thalassemia Membranopathies: • Spherocytosis • Elliptocytosis Enzymopathies: • G6PD Deficiency • Pyruvate Kinase Deficiency 71 Hematology Hemolysis Workup 1st line investigations for hemolysis: • Markers of RBC hemolysis: o Elevated LDH o Elevated indirect bilirubin o Low haptoglobin • Peripheral blood smear: o Markers of hemolysis on smear are schistocytes and spherocytes o Spherocytes are seen in warm autoimmune hemolytic anemia o Schistocytes are seen in most other causes of hemolytic anemia, particularly microangiopathic hemolytic anemias (MAHAs) such as HUS-TTP and DIC. 2nd line investigations for hemolysis: • DAT (aka. Coombs test): o Positive in autoimmune hemolytic anemia o This test does not need to be ordered routinely in workup of hemo- lysis unless there is a strong initial suspicion for autoimmune hemolytic anemia ____________________________________________________________________________________________________________________________________________________________________ Hemolytic Anemia ____________________________________________________________________________________________________________________________________________________________________ The Short List - Hemolysis 1. HUS-TTP 2. DIC 3. Autoimmune hemolytic anemia 4. Transfusion reaction
  • 73. DDx of ThrombocytopeniaDDx of Thrombocytopenia Decreased production Neoplastic: • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic syndrome • Metastatic disease Infectious: • Sepsis • Tuberculosis • HIV • Infectious mononucleosis Drug induced: • Chemotherapy • Alcohol Nutritional deficiencies: • Folate • B12 Other: • Liver disease DDx of ThrombocytopeniaDDx of Thrombocytopenia Increased destruction • Heparin Induced Thrombocytpenia (HIT) • Hemolytic-Uremic Syndrome (HUS) • Thrombotic Thrombocytopenic Purpura (TTP) • Disseminated Intravascular Coagulation (DIC) • Idiopathic Thrombocytopenic Purpura (ITP) • Antiphospholipid syndrome (APS) • SLE Sequestration • Splenomegaly 72 Hematology The Short List - Thrombocytopenia 1. Sepsis 2. Alcoholism 3. Liver disease 4. Splenomegaly 5. HIT 6. HUS/TTP, DIC 7. ITP ____________________________________________________________________________________________________________________________________________________________________ Thrombocytopenia ____________________________________________________________________________________________________________________________________________________________________
  • 74. DDx of PancytopeniaDDx of Pancytopenia Primary bone marrow etiologies Drugs & Toxins: • Chemotherapy • Radiation • Alcohol • NSAIDs • Sulfonamides (TMP-SMX) • Antiepileptic drugs (felbamate) • Chloramphenicol • Cimetidine • Benzene Infectious: • Hepatitis • HIV • EBV • Parvovirus B19 Neoplastic: • Leukemia (particularly acute leukemias) • Myelodysplastic syndrome • Myelofibrosis • Metastases from solid tumor to marrow DDx of PancytopeniaDDx of Pancytopenia Systemic disease with secondary bone marrow effects Immune disorders: • SLE • Sjogren’s syndrome • Graft versus host disease Nutritional deficiencies: • Vitamin B12 • Folate Other: • Sepsis • Splenomegaly • Pregnancy Congenital diseases: • Fanconi’s anemia • Storage diseases (Gaucher’s, Niemann-Pick) 73 Hematology Notes: • Aplastic anemia is characterized by diminished or absent hematopoietic precursors in the bone marrow, most often due to injury to the pluripotent stem cell. • The designation "aplastic anemia" is a somewhat of a misnomer because the disorder is defined as pancytopenia rather than anemia alone. ____________________________________________________________________________________________________________________________________________________________________ Pancytopenia ____________________________________________________________________________________________________________________________________________________________________
  • 75. DDx of CoagulopathyDDx of Coagulopathy Increased INR (extrinsic pathway) • Warfarin • Vitamin K deficiency • Liver disease (acute liver failure or cirrhosis) • Factor VII deficiency/Factor VII inhibitor • Rat poison Increased PTT (intrinsic pathway) • Heparin • Hemophilia A or B • Deficiency or inhibitor of intrinsic factors • Lupus anticoagulant • Von Willebrand’s disease Increased INR & PTT • Liver disease (acute liver failure or cirrhosis) • Disseminated intravascular coagulation (DIC) • Combined heparin and warfarin • Factor II, V, or X inhibitors 74 Hematology Notes - Nomenclature • Coagulopathy and bleeding diathesis are often used interchangeably to describe an unusual susceptibility to bleeding (hemorrhage) due to a de- fect in the system of coagulation. However, the term bleeding diathesis often includes reference to underlying platelet dysfunction, whereas the term coagulopathy is more specific to defects in INR & PTT. ____________________________________________________________________________________________________________________________________________________________________ Coagulopathy/Bleeding Diathesis ____________________________________________________________________________________________________________________________________________________________________
  • 76. DDxof Hypercoagulability /ThrombophiliaDDxof Hypercoagulability /Thrombophilia Acquired Antiphospholid Antibody Syndrome (APS): • Lupus Anticoagulant • Anticardiolipin Antibodies • Beta2-glycoprotein-I Antibodies Other hematological causes: • Heparin induced thrombocytopenia (HIT) • Disseminated intravascular coagulation (DIC) • Paroxysmal nocturnal hemoglobinuria (PNH) • Polycythemia vera • Essential thrombocytosis Systemic disease: • Malignancy • Inflammatory bowel disease • Nephrotic syndrome • HIV/AIDS Drugs: • Oral contraceptive pills (OCPs) • Hormone replacement therapy (HRT) Other: • Pregnancy • Immobilization • Surgery/Trauma DDx of Hypercoagulability /ThrombophiliaDDx of Hypercoagulability /Thrombophilia Inherited Always detectable: • Factor V Leiden mutation • Prothrombin gene mutation Must be off anticoagulation for detection: • Antithrombin deficiency • Protein C & S deficiency 75 Hematology The Short List - Thrombophilia 1. Immobilization/Surgery/Trauma 2. Malignancy 3. OCPs 4. APS 5. HIT 6. Inherited thrombophilias ____________________________________________________________________________________________________________________________________________________________________ Hypercoagulability/ Thrombophilia ____________________________________________________________________________________________________________________________________________________________________
  • 77. 76 Hematology Notes • Thrombophilia is a hereditary or acquired predisposition to develop blood clots. These blood clots can be either arterial or venous thrombosis. • Note that the differential on the previous page is for venous thrombosis. Causes of both venous and arterial thrombosis are seen in: Major Causes of Arterial & Venous Thrombosis • Antiphospholipid Syndrome (APS) • Heparin induced thrombocytopenia (HIT) • Disseminated intravascular coagulation (DIC) • Paroxysmal nocturnal hemoglobinuria (PNH) ____________________________________________________________________________________________________________________________________________________________________ Hypercoagulability/ Thrombophilia ____________________________________________________________________________________________________________________________________________________________________ Lab Workup - Hypercoagulability • Routine workup of a new diagnosis of thrombosis without obvious precipi- tant may include the following: o Lupus anticoagulant & anticardiolipin o Factor V Leiden o Prothrombin gene mutation o Antithrombin levels o Protein C& S levels • Antithrombin levels measured in the blood are decreased when there is thrombosis present or when the patient is given heparin. Protein C & S lev- els are decreased by warfarin. • Therefore, when measuring the levels of Antithrombin, Protein C, and Pro- tein S, it is necessary that the patient be off anticoagulation and that there be no evidence of thrombosis. • Furthermore, it is important to note that antithrombin and protein C&S are acute phase reactants, hence can be elevated during acute illness.
  • 78. ______________________________________________________________________________ Elevated LDH (Lactate Dehydrogenase) ____________________________________________________ DDx of Elevated LDHDDx of Elevated LDH Cell Lysis • RBC Hemolysis • Tumor Lysis Syndrome • Rhabdomyolysis • Acute liver injury • Lymphoma (rapid cell turnover) Infectious • Pneumocystis jiroveci (PJP) Cardiac • Myocardial Infarction Obs-Gyn • Dysgerminoma ______________________________________________________________________________ Elevated D-dimer ____________________________________________________ 77 Hematology Notes • LDH is an intracellular enzyme found in most cells, involved in the Krebs cycle.. • Any injury leading to cell breakdown or lysis will release LDH into the bloodstream, and hence can theoretically account for an elevation in LDH levels. • LDH is a very non-specific enzyme found to be elevated in many condi- tions, however the levels are often significantly elevated when there is un- derlying cell lysis. • When levels of LDH are seen in the thousands, you should particularly investigate and aim to rule out RBC hemolysis, tumor lysis, rhadbomyoly- sis, acute liver injury, and lymphoma. Notes: • The utility of ordering a D-dimer test is limited to excluding DVT or PE in patient at low probability as per their Well’s score. • This is due to the fact that D-dimer is extremely sensitive for DVT and/or PE, with a sensitivity between 85 and 95% based on which assay the lab at your facility uses. • The other major use in ordering a D-dimer is when you are suspecting DIC. DDx of Elevated D-dimerDDx of Elevated D-dimer Thromboembolic disease Any venous or arterial thrombus, particularly: • Deep venous thrombosis • Pulmonary embolism Cardiac • Myocardial infarct • Congestive heart failure • Atrial fibrillation Renal • Acute renal failure • Chronic kidney disease • Nephrotic syndrome Other • Severe infection/sepsis • Inflammation • Malignancy • Liver disease • Surgery • Trauma • Pregnancy