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MEDICO NOTES LECTURES OFINTERNAL MEDICINE Third Editio | INTERNAL1-17AFEEF-MERGED-1.pdf |
Table of content Copyrights@ Disclaimer Table of content Table of tables Table of Figures Nephrology The kidney function test (KFT) Arterial blood gases Acute kidney injury (AK!) Introduction to the glomerular diseases Disorders of nephrotic syndrome Disorders of nephritic syndrome Chronic Kidney disease (CKD) Cystic diseases of the kidney Electrolyte disturbances Inherited defects of the nephron HTN Endocrinology Introduction to the Endocrinology The pituitary gland The Thyroid gland Parathyroid gland Adrenal gland Diabetes mellitus (DM) Hypoglycemia Other endocrine disorders Pulmonologyiv viii xi 11 19 23 30 35 41 44 47 48 49 56 62 72 83 85 91 Page Ixi | INTERNAL1-17AFEEF-MERGED-1.pdf |
Pulmonary Function Test (PET) Obstructive lung diseases Interstitial lung diseases (ILD) Respiratory infections Pleural diseases Other respiratory disorders Cardiology Diseases of the heart conduction Diseases of the myocardium Diseases of Endocardium Pericardial diseases Other cardiology problems Gastroenterology Introduction to gastroenterology Disorders of the esophagus Stomach and Small intestine Disorders of the large intestine Hepatology Introduction to hepatology Acute liver diseases Chronic liver diseases Complications of liver cirrhosis Liver storage diseases Hematology Introduction to Hematology Blood products and transfusion Anemia of reduced RBC production Anemia of high RBC destruction92 95 105 110 119 122 129 130 143 164 172 175 177 178 179 184 200 207 208 212 218 224 228 231 232 242 245 254 Pagelxii | INTERNAL1-17AFEEF-MERGED-1.pdf |
Disorders of primary hemostasis Disorders of secondary hemostasis Myeloproliferative disorders Malignant white cell disorders Rheumatology Introduction to Rheumatology Raynaud's disease &ythema nodosum Stevens-Johnson syndrome (SJS) Rheumatoid arthritis (RA) Systemic lupus erythematosus (SLE) Antiphospholipid syndrome (APS) Systemic sclerosis (SS) Sjögren's syndrome Mixed connective tissue disease (MCTD) Spondyloarthropathies Osteoarthritis (OA) Neuropathic joint (Charcot joint) Infective arthritis Crystal-induced arthropathies Vasculitis Dermatomyositis fibromyalgia Neurology Introduction to neurology Thunderclap headache Headache Syndromes Acute stroke265 270 276 279 291 292 295 296 297 298 302 305 306 307 308 308 312 314 315 317 320 323 324 325 326 331 333 337 Page Ixiii | INTERNAL1-17AFEEF-MERGED-1.pdf |
Epilepsy Status Epilepticus Essential tremor Dementia Parkinson's disease (PD) Alcoholic encephalopathies Neurological autoimmune disorders Amyotrophic lateral sclerosis (ALS) CNS infections Organophosphate poisoning Common ENT conditions Infectious diseases Principles of microbiology Pyrexia of unknown origin (PUO) Bacterial infections Viral infections Sexually transmitted diseases Common parasites Clinical pharmacology Drugs and their antidotes Antibiotics Drugs used in DM Common cardiac medications Gl medications Analgesics Corticosteroids Cyclosporine339 341 341 342 344 345 346 349 352 354 357 358 359 360 367 372 375 379 386 392 394 395 396 P age Ixiv | INTERNAL1-17AFEEF-MERGED-1.pdf |
Table of tables Table 1: Cockcroft-Gault equation for GFR Table 2: Tubular vs Glomerular proteinuria Table 3. Serum and urine anion gap Table 4: The estimated HC03 and Pa C02 in gas disorders Table 5. Pre-renal azotemia vs ATN Table 6: Summary of Tubular diseases Table 7:Primary and secondary glomerular diseases Table 8: PSGN vs. lg A nephropathy Table 9:c ANCA vs. p ANCA Table 10:WHO classification for lupus nephritis Table 11. CKD stages according to GFR Table 12. Types of renal osteodystrophy Table 13. Indications for hemodialysis Table 14: Acute on top of chronic renal failure Table 15:Acute vs. Chronic renal failure Table 16: Water deficit calculation Table 17:Sodium deficit calculation Table 18. common IV fluids and their compositions per liter Table 19:anti-hyperkalemia protocol Table 20. Laboratory features of RTA types Table 21. Genetic syndromes that affect the renal tubules Table 22. Important points about renal artery stenosis Table 23:The drug of choice for HTN in specific groups Table 24. Features of DIDMOD syndrome Table 25:disorders of thyrotoxicosis and their unique features Table 26. Hypothyroidism vs. Hyperthyroidism Table 27:Pseudohypocalcemia and corrected calcium Table 28: Differential diagnosis of parathyroid disorders Table 29. Lab tests in primary hypoadrenalism Table 30: Comparison between Tl DM vs. T2DM Table 31 : Glucose investigations and their ranges Table 32. Health maintenance for all DM patients Table 33: DKA vs. HHS Table 34: Treatment of hypoglycemia in babies10 15 18 19 25 27 31 31 32 32 32 42 43 45 45 54 59 63 66 69 74 76 77 Pagelxv | INTERNAL1-17AFEEF-MERGED-1.pdf |
Table 35: Types of Multiple Endocrine Neoplasia (MEN) Table 36 Normal and abnormal values of BMI for adults Table 37. Obstructive vs. Restrictive lung diseases Table 38. causes of high vs. low DLco Table 39. Causes of hypoxia according to the A-a gradient Table 40: Asthma classification according to the severity Table 41 : classification of acute asthma exacerbation Table 42: Asthma controllers and relievers medications Table 43. Staging of COPD Table 44: Indications for LTOT Table 45:causes of Upper vs. Lower lobe lung fibrosis Table 46: Typical vs. atypical pneumonia Table 47: Differential diagnosis of pneumonia Table 48: CURB65 score for pneumonia prognosis Table 49:indications for the pneumococcal vaccine Table 50:Mantoux test interpretation Table 51. the side effects of Anti-TB medications85 93 94 94 96 98 100 100 102 105 111 111 112 113 117 118 Table 52. Causes of Exudative and Transudative pleural effusion. 119 Table 53:Modified fights criteria Table 54. causes of Type 1 vs. Type 2 respiratory failure Table 55:Axis deviation interpretation in ECG Table 56: ECG changes in different conditions Table 57: CA2DS2 VAS scoring system Table 58: Causes of long QT syndrome and Td P120 125 131 132 135 138 Table 59: the ECG changes in the different degrees of AV block 140 Table 60: CABG indications and graft used Table 61 : Types and contraindications of stress test Table 62: Stable vs. Unstable angina Table 63: TIMI score for UA and NSTEMI Table 64: Complicafions of myocardial infarction Table 65: BNP rule in the diagnosis of SOB Table 66: Heart sounds and their causes Table 67: Features and causes of different types of Pulses Table 68: Causes of different types of heart murmurs145 146 147 151 154 157 169 170 170 Table 69: Doses of adrenalin and hydrocortisone in anaphylaxis. 175 Page Ixvi | INTERNAL1-17AFEEF-MERGED-1.pdf |
Table 70: The differential diagnosis of epigastric pain 184 Table 71:Different types of H. pylori tests 188 Table 72. Gastric vs. Duodenal ulcer 189 Table 73. Rockall Score for risk of death in upper GI bleeding 192 Table 74. The sites for absorption of different nutrients 194 Table 75: Causes of bloody vs. non-bloody diarrhea 196 Table 76. differences between IBD types 200 Table 77. Clinical features of CD vs. UC 201 Table 78: Extraintestinal manifestations in CD and UC 201 Table 79: Complications of CD vs. UC 202 Table 80: Treatment of UC203 Table 81: treatment of CD203 Table 82:Alarm symptoms for IBS 205 Table 83:Bilirubin metabolism210 Table 84: General information about hepatitis viruses 212 Table 85:HBV markers interpretation 214 Table 86: Poor prognostic factors of FHF 217 Table 87:Poor prognostic factors of paracetamol-induced fiver failure217 Table 88: Child-Pugh score for liver cirrhosis 219Table 89: PBC vs. psc222Table 90: Differential diagnosis of ascites 224 Table 91 : the laboratory tests used in assessing hemostasis 233Table 92: The clotting factors affecting PT and PIT 233Table 93: Clotting factors names and numbers 233Table 94: Blood film interpretation236Table 95: Unfractionated vs. LMWH 237Table 96: warfarin-induced skin necrosis 238Table 97: Warfarin drug interactions 239Table 98: Heparin vs. Warfarin240Table 99: Causes of anemia according to the MCV 246Table 100: The normal dietary allowance of iron 246Table 101: Expected lab tests in IDA 247Table 102: Vitamins B12 vs. folate 251Table 103: schilling test interpretation (Low: < 3%, Normal: > 7%)..254 Page Ixvii | INTERNAL1-17AFEEF-MERGED-1.pdf |
Table 104: Causes of Intravascular and Extravascular hemolysis..254 Table 105: Expected lab results in hemolytic anemia 255 Table 106: Warm vs. cold AIHA 263 Table 107. Types of HIT syndrome 267 Table 108. Interpretation of the blood test results 272 Table 109. Virchow's triad (the risk factors for hypercoagulability) 272 Table 1 10:Difference between normal and thrombosed veins.... 273 Table 1 1 1: Well's Criteria, A scoring system for the diagnosis of PE275 Table 112. Causes of massive splenomegaly Table 113. Ann-Arbor staging of lymphoma Table 1 14:Hodgkin vs. Non-Hodgkin lymphoma Table 15:Side effects of the lymphomas drugs Table 116. Common gene translocations in hematology Table 1 17:Diagnostic criteria for multiple myeloma Table 118. Classifications of arthritis Table 119. Joint aspiration rule in different types of arthritis Table 120. The acute phase reactant; CRP Table 121: autoantibodies and their associated disorders Table 122. Types of hypersensitivity282 285 286 286 287 288 292 292 293 293 294 Table 123: different HLA types and the associated disorders........294 Table 124: Raynaud's Phenomenon 296 Table 125: Stevens-Johnson vs. Toxic Epidermis Necrolysis 297 Table 126: The diagnostic criteria for RA 298 Table 127: DMARDs and their side effects 302 Table 128: antibodies associated with SLE 303 Table 129: causes of markedly elevated or markedly low ESR......322 Table 130: the cranial nerves 328 Table 131: UMNL vs. LMNL Table 132: types of deep tendon reflexes and their nerve roots... 330 Table 133: Differential diagnosis of Thunderclap headache......... 331 Table 134: The red flags (alarm symptoms) of headache 331 Table 135: Differential diagnosis of Headache syndromes Table 136: ABCD2 score for TIA patients 338 Table 137: Antiepileptic drugs (AEDs) and their indications 340 Table 138: The most common causes of meningitis P age Ixviii | INTERNAL1-17AFEEF-MERGED-1.pdf |
Table 139: CSF interpretation for meningitis patients 351 Table 140: Empirical antibiotic treatment in meningitis 351 Table 141 : Systemic effects of Organophosphate poisoning 353 Table 142: Species of brucella and their most common sources..360 Table 143: WHO recommendations for tetanus vaccine (TV) and tetanus immunoglobulin administration Table 144: Diseases affecting HIV patients Table 145. Species of Plasmodium and their characteristics Table 146: Common drugs and their antidotes Table 147: antibiotics classification and their site of action Table 148. antibiotic classification and their type of action Table 149: cephalosporine generations Table 150. the bacterial coverage in cephalosporines Table 151:Antipseudomonal agents Table 152. The different types of insulin365 374 376 381 381 383 385 387 Page Ixix | INTERNAL1-17AFEEF-MERGED-1.pdf |
Table of Figures Figure 1: Physiology of renin-angiotensin system Figure 2: IVP showing Ring shadow Figure 3: RBC cast in urine consistent with glomerulonephritis Figure 4: A characteristic rash of HSP Figure 5: ECG changes in Hyperkalemia Figure 6: Treatment approach for HTN Figure 7: Example of the negative feedback Figure 8: Diagnostic approach to Cushing's syndrome Figure 9: Mnemonics for MEN types Figure 10: The normal lung volumes for a healthy 70 kg male Figure 1 1: A stepwise approach to asthma control Figure 12: (a) normal chest X-Ray, (b) Hyperinflated chest Figure 13: A chest X-ray showing Air fluid level (Lung abscess) figure 14: chest X-Ray showing bilateral pleural effusion Figure 15: Different types of Chest deformities figure 16: the heart conduction system Figure 17: strep rhythm ECG showing sinus tachycardia Figure 18: strep rhythm ECG showing sinus bradycardia figure 19: strep rhythm ECG showing Sick Sinus Syndrome Figure 20: a strep rhythm ECG showing Atrial fibrillation figure 21: the approach for Atrial fibrillation treatment figure 22: a strep rhythm ECG showing Atrial flutter figure 23: A strep rhythm ECG showing MAT figure 24: A strep rhythm ECG showing SVT21 28 46 49 68 85 93 97 101 118 120 127 130 133 133 134 134 135 136 136 137 figure 25: A strep rhythm ECG showing Ventricular tachycardia. 137 Figure 26: A strep rhythm ECG showing Torsade de points Figure 27: A strep rhythm ECG showing Bigeminy Figure 28: A strep rhythm ECG showing Ventricular Fibrillation Figure 29: A strep rhythm ECG showing Delta wave figure 30: anatomy of the coronary artery figure 31: One beat ECG showing epsilon wave Figure 32: A sketch showing an Atrial myxoma Figure 33: a) Osler nodes, B) Janeway lesions, C) Roth spots Figure 34: Pericardiocentesis procedure138 138 139 139 150 162 163 165 173 Page Ixx | INTERNAL1-17AFEEF-MERGED-1.pdf |
Figure 35: A sketch showing the alimentary tract Figure 36: A sketch showing achalasia figure 37:The gastric acid secretion and drugs effect on it Figure 38. The suspensory Ligament of Treitz Figure 39: The liver and biliary tree Figure 40: Bilirubin metabolism and excretion178 182 185 190 208 210 Figure 41 : The coagulation cascade in secondary hemostasis..... 232 Figure 42: The normal hematopoiesis 234 Figure 43: Hand Joints deformities in Rheumatoid Arthritis 299 Figure 44. Anatomy of the sacroiliac joint Figure 45: Joint X-Ray shows Chondrocalcinosis figure 46: Erythema migrans in Lyme disease309 319 363 Page Ixxi | INTERNAL1-17AFEEF-MERGED-1.pdf |
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Nephrology CHAPTER 1 AM JAD K. ALAFEEF Phone number: +962798843824 E-mail: Afeeef. 2005@gmail. com Page Il | INTERNAL1-17AFEEF-MERGED-1.pdf |
The kidney function test (KFT) functions of kidneys Excretion of waste products and drugs Regulai body fluid Secretion erythropoietin, renin prostaglandins Metabolism of Vitamin D Urea and creatinine The serum urea (Ur): Urea (Ur) is product of protein catabolism, filtered by nephron and 30 — 70% reabsorbed back in blood Blood urea nitrogen (BUN) is nitrogenous content of urea; it equals serum urea aivided by 2. 14 uremia and azotemia are related to renal impairment. Azotemia is the presence of nitrogenous substances in the blood, while uremia is the presence of urea. The serum creatinine (Cr): Creatinine (Cr) is product of muscle destruction and is freely excreted but not reabsorbed by nephron A reduction or loss of muscle mass because of advanced age, liver failure, or malnutrition may cause a relatively lower serum creatinine concentration. In these scenarios, the serum creatinine and GFR will overestimate kidney function. BUN to Creafinine ratio (BUN/Cr): normal BUN to Cr ratio is 20:1 In dehydration, urea will increase while creatinine remains normal. Therefore, if the ratio becomes > 20: l, the cause is pre-renal (renal hypoperfusion) If the BUN:Cr ratio is 20:1 or less, intra-renal or post-renal pathologies are the causes. Page 12 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Glomerular filtration rate (GFR) GFR measures the amount of plasma filtered across the glomerular capillaries. normal daily GFR is 100 — 120 ml/min At high levels of GFR, small changes in serum creatinine level will reflect a large change in the GFR and vice versa in the low levels. GFR is reduced in acute and chronic renal failure Serum urea and creatinine do not rise in the case of renal failure until a 50 60% reduction of GFR; so normal urea and creatinine do not exclude renal insufficiency GFR calculation: (there are 3 equations) The Cockcroft-Gault equation is the least accurate one Modification of Diet in Renal Disease (MDRD) study equation performs best when GFR is <60 m L/min/l. 73 m2 Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation performs better at near-normal GFR values [(140 — age) * body weight 0. 85 for femalel / (72* creatinine mg/dl) Table l: Cockcroft-Gault equation for GFR Urinary protein Normal and abnormal protein in urine: It is normal to excrete a tiny amount of protein (known as Tamm-Horsfall protein) (normal daily loss of < 150 mg/day) Proteinuria indicates tubular or glomerular disease; severe proteinuria g/day) indicates glomerular diseases. When significant proteinuria is encountered, renal biopsy should be done to determine the etiology Causes of proteinuria: Transient proteinuria: o Postural or orthostatic proteinuria: occurs in upright positions only o Non-postural: (Fever, Vigorous exercise, Seizure, etc. ) Persistent proteinuria: could be glomerular or tubular causes. Page 13 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Pathology Amount Albuminuria Associations Detection:Tubular Low reabsorption < I gm/ day Absent Glomerular High permeability Can be > I gm/ day Present Glucosuria, phosphaturia Edema, HTN, hematuria Table 2: Tubular vs Glomerular proteinuria Urine dipstick: o Albumin is the only protein detected on dipstick urinalysis. o Less sensitive: Reported as (+1: 30 mg/dl), (+2: 100 mg/dl), (+3: 300 mg/dl), (+4:-2000 mg/dl). 24 hours urine collection: Normal < 150 mg/day: o Renal function usually varies during the day, and transient proteinuria is present in 2— 10% of the population, so 24 urine collection for protein is more accurate than spot urinary protein measurement. o Heavy proteinuria > lg / day (Glomerular origin) o Nephrotic range proteinuria > 3. 5 g/day Urine protein/creatinine ratio (P/Cr ratio): o Recent evidence indicates that the P/Cr ratio is more accurate than the 24-hour urine protein measurement (The P/Cr ratio is easier and faster to perform) o The P/Cr ratio is equivalent to the number of grams in the 24-h collection; a ratio of less than 0. 2 is equivalent to 0. 2 g of protein per day, and the ratio of 3. 5 is equivalent to 3. 5 g of protein per day and is considered nephrotic-range. Albumin/creatinine ratio (ACR): o Measures only the albumin in the urine and is used to evaluate diabetic kidney disease o It should be done annually for all diabetic patients o Early morning specimens should be used o ACR > 2. 5 is considered microalbuminuria Urinary immunoelectrophoresis o It is a urine test that measures the immunoglobulins in a urine sample o It is used to detect Bence-Johns Protein (BJP) in case of multiple myeloma Page 14 | INTERNAL1-17AFEEF-MERGED-1.pdf |
The routine urinalysis It has 2 parts (dipstick and microscopic analysis)Color: normally yellow, darker if dehydrated, and white ifwell hydrated. It also can be red-colored if RBCs, myoglobin,or Hb are present and can be turbid or green if there is aninfection Volume: o Anuria: if less than 100 ml/day o Oliguria: if less than 500 ml/day o Polyuria: if more than 3 liters/day Specific gravity: normally 1. 002 to 1. 025 o Reflects the number of particles in the urinecompared to the water content. o It will be high in dehydration and DM but low in DIand chronic renal failure. Urinary PH: the normal value is 6 o Urine will be alkaline in Proteus infectiono If early morning urine is alkaline, consider distal RTAUrine glucose: usually indicates DM, but it is falsely positive inpregnancy, vitamin C intake, tetracycline or levodopa use Urinary ketones: can present in DKA or due to starvation Urine protein: proteinuria indicates a glomerular or tubulardisease Findings in the urinary microscopy: o WBC of > 10 hpf indicates UTI o For persistent high urine WBCs with negative culture,consider genitourinary TB. o RBCs of > 5 hpf indicate hematuria Page 15 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Physiology of the renin-angiotensin system Whenever there is hypoperfusion to the renal artery, renin hormone is secreted by the Juxtaglomerular apparatus of the nephron Renal hypoperfusion Angiotensinogen Renin Angiotensin I ACE Angiotensin-converting enzyme (ACE) Angiotensin Il Secretion of aldosterone; sodium, and water retention Sympathetic activation; arterial vasoconstriction Sodium, chloride, and water reabsorption with potassium excretion Release of ADH from the pituitary gland; water reabsorption Figure l: Physiology of renin-angiotensin system Page 16 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Arterial blood gases Arterial blood gas is a test that estimates the blood PH, C02, 02, HCOs, electrolytes, and many other variants. Arterial samples, mostly from the radial artery, should be tested in a special machine to evaluate ABCs. Quick points about ABGs reading The PH: is an indicator of the blood acidity o Normal blood PH: 7. 35 — 7. 45 o PH of less than 7. 35 indicates acidosis o PH of more than 7. 45 indicates alkalosis The Pa C02: is an acid controlled by the lungs o Normal value: 35 — 45 mm Hg o Hyperventilation causes a C02 wash leading to alkalosis o Hypoventilation causes C02 retention leading toacidosis The HC03-: is an alkaline, metabofically controlled by renaland Gl systems o Normal value: 22 — 28 meq/L o Decreased HC03will lead to acidosiso Increased HC03-wil I lead to alkalosis Steps for ABGs Reading: Step 1: Look for PH: o If PH is high (> 7. 45), the answer is alkalosiso If PH is low (< 7. 35), the answer is acidosis Step 2: Look for Pa C02'. o If it changes in the same direction as PH, it ismetabolic o If it changes in the opposite direction, it is respiratory Step 3: look for compensations and mixed disorders. Page 17 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Respiratory acidosis It is defined as the increase in the Pa C02 that leads to decreased blood PH. Causes: (any cause of hypoventilation) Primary lung diseases like COPD, OSA, and life-threatening asthma. Neuromuscular disorders: e. g., myasthenia graves, kyphoscoliosis CNS disorders: opiate overdose, brainstem lesions Drug-induced hypoventilation: e. g., opiates Respiratory alkalosis It is defined as C02wash (Decreased Pa C02) that leads to elevated blood PH. Causes: (any cause of hyperventilation) Anxiety (hysterical hyperventilation) Pain and fever Anemia Interstitial lung disease Pulmonary embolism Mild Asthma In respiratory acidosis and alkalosis, minute ventilation is more important than the respiratory rate (Minute ventilation equa\s the respiratory rate multiplied by the tidal volume) Hyperventilation syndrome: when a patient is exposed to stress, he starts to hyperventilate, feeling unwell, then more hyperventilation develops. Respiratory alkalosis is a feature A patient may develop symptoms like chest pain, numbness, and weakness Treat the patients by making them breathe into a bag to reduce the C02 wash Page 18 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Metabolic acidosis It is defined as the reduced plasma PH and Plasma HCOs A high anion gap indicates metabortc acidosis even if PH,Pa C02, and HC03-are normal. The anion gap: In metabolic acidosis, always measure the anion gap todetermine the differential diagnosis. Serum anion gap = (Na) — (Cl + HC03-) Urine anion gap = urine Na — urine Cl Wide anion gap means Anion gap of > 12The most important causes of normal anion gapmetabolic acidosis are diarrhea and RTA RTA has a positive urine anion gap, but diarrhea has anegative urine anion gap Table 3: Serum and urine anion gap Causes of anion gap metabolic acidosis (MUD PILS): Methanol overdose Uremia: renal failure DKA Phosphate, paraldehyde, propylene glycol Ischemia Lactate: hypotension, hypoperfusion Starvation, Salicylate overdose Causes of non-anion gap metabolic acidosis (HARDASS): Hyperalimentation Addison's disease Renal tubular acidosis (RTA) Diarrhea, ileostomies, fistula. Acetazolamide Spironolactone Saline infusion Page 19 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Metabolic alkalosis Defined as elevated PH and serum bicarbonate levels Causes: Gl loss of acid: vomiting, NG tube suction Increased aldosterone: Conn's, Cushing's Diuretics and Hypokalemia Milk-alkali syndrome: high volume liquid antacids ABGs compensation Whenever the blood has alkalosis or acidosis, the buffering system in the body tries to return the PH into its normal range by a process called compensation. Metabofic acidosis and alkalosis are compensated by the C02 by changing the respiratory rate, while respiratory acidosis and alkalosis are compensated by changing HCG'. C02compensation is rapid, but HC03 compensation usually takes up to 48 — 72 hours, so respiratory problems with metabolic compensation indicate that the etiology is longer than 48 hours. When the PH and the HCG-are reduced in metabolic acidosis, the lung will hyperventilate to washout C02and make PH return to normal. In pure metabolic acidosis, Winters' formula predicts that C02 should be I. 5 times the bicarbonate concentration plus 8 ± 2 mm If the Pa C02 is more than predicted, additional respiratory acidosis is present, while if the Pa C02 is less than predicted, additional respiratory alkalosis is present. Disorder Metabolic acidosis Metabolic alkalosis Acute respiratory acidosis Chronic respiratory acidosis Acute respiratory alkalosis Chronic respiratory alkalosis Estimated change (A) Pa C02 = [l HC03-+8] ± 2 A HCOF A Pa C02* 0. 7 A Pa C02 = 10 * A in HC03-A Pa C02 = 3. 5 * A in HC03-Change in Pa C02 = 5* A of HC03-Change of Pa C02 = 2 * A in HCOS Table 4: The estimated HC03 and Pa C02 in gas disorders Page 110 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Triple acid-base disorder estimation Delta — Delta: Delta — Delta = A anion gap/ A bicarbonate A Anion Gap = Anion Gap— 10 A Bicarbonate level = Bicarbonate level — 24 The normal Delta — Delta is 1 —2 If Delta Delta < 1, consider concurrent normal anion gapmetabofic acidosis If Delta Delta > 2, consider concurrent metabolic alkalosis Acute kidney injury (AKI) Acute renal failure or AKI is an acute reversible deteriorationof renal function that develops within days. Causes: It can be one of three types: Pre-renal type (decreased renal perfusion) Parenchymal type (ischemia or toxin affecting kidney tissue):o Acute tubular necrosis (ATN) o Acute glomerulonephritis o Acute interstitial nephritis o Vascular cause Post-renal type (obstruction) Clinical features: There is no pathognomonic physical finding to diagnose AKIwithout lab investigations. The patient may have anasymptomatic increase in urea and creatinine or presentwith non-specific symptoms like nausea, vomiting, malaise,weakness, and shortness of breath. Abnormalities of the urine volume (anuria, oliguria, orpolyuria) Very severe disease may present with confusion, arrhythmiadue to hyperkalemia, or uremic pericarditis. Lab abnormalities: o Azotemia: the rise of BUN and serum creatinine levelswith the reduction of the CFRo Electrolyte disturbance (hyperkalemia, hyponatremia,hyperphosphatemia, and hypocalcemia) Page | INTERNAL1-17AFEEF-MERGED-1.pdf |
Pre-renal AKI It is a reversible kidney injury resulting from decreased blood perfusion to the kidneys It is the most common type of acute renal failure (70%) It is caused by any cause of decreased renal artery perfusion; e. g., decreased cardiac output, dehydration, sepsis, shock, burns, or renal artery stenosis If it persists without treatment, intrinsic renal failure occurs Clinical features: History of fluid loss followed by decreased urine output (e. g., burn, vomiting, diarrhea, etc. ) Hypotension, decreased urine output Signs and symptoms of the cause. Diagnosis: Serum BUN:Cr ratio > 20: I Urine sodium < 20 m Eq/l Low Fractional sodium excretion (FENa) < 1% Urine osmolality > 500 m Osm/kg High specific gravity (concentrated urine) In pre-renal AKI, there will be: Decreased blood pressure increased aldosterone increased sodium reabsorption-4 decreased urine sodium. Decreased intravascular volume —+ increased ADH increase water reabsorption —+ concentrated urine with high osmolality > 500 m Osm/kg Treatment: The priority is to restore the renal blood flow by IV fluids Correction of the cause to prevent further deterioration Maintain electrolytes normal Avoid nephrotoxic medications during the illness. Page 112 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hepatorenal syndrome It is a renal failure developed secondary to liver disease Two main types: Type 1 (acute) and type 2 (gradual)Caused by splanchnic vasodilatation and reduced totalsystemic vascular resistance Very poor prognosis with high mortality. Clinical features: New onset of renal failure in a patient with severe liverdisease Absence of any other explanation for the renal failure Investigations: goes with pre-renal AKI Low urine sodium < 15 m Eq/l FENa < 1% Elevated BUN/Creatinine ratio Treatment: Midodrine and octreotide increase the mean arterialpressure and reduce the splanchnic vasodilatation Noradrenaline to increase the mean arterial pressure Transjugular intrahepatic portosystemic shunt (TIPSS) willprovide a short-term benefit Renal replacement therapy Intrinsic Renal AKI Acute tubular necrosis (ATN) It is the most common form of intrinsic renal failure It characterized by tubular cell damage It can be reversible if appropriate management (tubularcells can regenerate) At may be of ischemic or nephrotoxic types Causes of ATN: Ischemic (if no adequate treatment of pre-renal AKI, it willtransform into ATN) Drugs: Aminoglycosides, amphotericin, vancomycin,cisplatin, acyclovir, cyclosporine, NSAl Dso Slow onset: need 5— 10 dayso Dose-dependent: the higher the dose, the more injuryo Low Mg level increases the risk of aminoglycoside and cisplatin toxicity. Page 113 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Contrast media: o Rapid effect o It can be prevented with normal saline hydration (the best choice) o N-acetylcysteine and sodium bicarbonate are not consistently proven benefits. o Only contrast media present with ATN with low urine sodium, FENa < 1%, and very high specific gravity. Hemoglobin (due to hemolysis), myoglobin (due to rhabdomyolysis) Hyperuricemia (from tumor lysis syndrome) Bence-Johns proteins in multiple myeloma. Clinical picture: There are 4 phases of ATN: Pre-oliguric phase (O —2 days): o It starts from the precipitating event until oliguria occurs o Symptoms of primary cause are dominant o This phase is reversible if circulation is restored early and completely Ofiguric phase (8 — 14 days) o Oliguria or rarely anuria o Water and electrolyte imbalances occur at this phase Diuretic phase (10 days) o The new epithelium cannot concentrate urine o Polyuria 3—5 liters per day leading to dehydration Recovery phase (4 —6 months): The period from the stabilization of serum laboratory values until the restoration of optimal renal function Diagnosis: History of toxin exposure is a clue Elevated kidney function test Urine chemistry shows high sodium, high FENa, and low osmolality. Treatment: Treatment of the reversible causes Maintenance of hydration and electrolyte balance Avoid nephrotoxic medications Hemodialysis as indicated Page 114 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Isosthenuria is the condition in which serum osmolalityequals urinary osmolality. It occurs in ATN because of thefailure of the tubular cells to concentrate urine. In contrast to pre-renal azotemia, ATN patients inappropriately lose sodium and water. o Urinary sodium will be > 40 mmol/l o Urine osmolality will be below 300 m Osm/l The parameter Urine sodium BUN/Creatinine FENa Fractional urea excretion Urine osmolality (m Osm/kg) Specific gravity Response to fluid replacement Pre-renal azotemia < 20 mmol/l > 20 < 35% > 500 > 1020 Yes FENa = (urine Na/plasma Na) / (urine Cr/plasma Cr) x 100ATN > 40 mmol/l 10-15 > 35% < 350 < 1010 no Fractional urea excretion = (urine Ur /blood I-Jr) / (urine Cr/plasma Cr) x 100 Table 5: Pre-renal azotemia vs ATN Rhabdomyolysis Rhabdomyolysis occurs due to severe destruction or necrosisof the muscles leading to a release of a large amount ofmyoglobin which has a toxic effect on renal tubules. Precipitants: Trauma, Crush injury, Prolonged immobility Drugs (e. g., Statins, Cocaine toxicity)Convulsions Snake Bites Heatstroke Clinical picture: History of precipitant Myalgia Dark urine (myoglobinuria) May present with arrhythmias or other electrolytedisturbance signs and symptoms Features of acute tubular necrosis (ATN) Page 115 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diagnosis: ECG is the most urgent step to do (to rule out arrhythmia secondary to hyperkalemia) Urinalysis: positive for blood in dipstick, but no cells will be seen in microscopy. Urine myoglobin (most accurate test) CPK very high Hyperkalemia (released from damaged cells) Hyperuricemia (nucleic acid released from broken nuclei and rapidly metabolized into uric acid) Hypocalcemia (calcium binds to phosphate and damaged muscles) Elevated urea and creatinine Treatment: Normal saline Mannitol and diuresis (decrease contact time of myoglobin to tubules) Bicarbonates (shift potassium to the intracellular compartment and prevent precipitation of myoglobin in tubules) No need to treat hypocalcemia in rhabdomyolysis Acute interstitial nephritis (AIN) Causes: Drugs (70%): penicillin, PPI's, phenytoin, cephalosporin, sulfa drugs, rifampicin, NSAl Ds, furosemide, quinolones, streptomycin, or allopurinol. Systemic diseases (SLE, sarcoidosis, multiple myeloma, Sjögren's syndrome) Infections (streptococci, TB, CMV) Medications that are associated with AIN are the same medications that are associated with drug allergy and rash, Steven-Johnson syndrome, toxic epidermal necrolysis, and hemolysis Presentation: Fever (80%), rash (50%), arthralgia Usually, non-oliguric acute renal failure History of drug hypersensitivity reaction Page 116 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Labs: KFT: Deterioration of renal function (BUN:Cr ratio < 20)CBC: Eosinophilia Urinalysis: High RBC, high WBC, WBC casts, proteinuria, eosinophiluria Treatment: Supportive treatment of acute renal failure Oral or IV cortisone (used if no improvement after removal ofprecipitating factor) Management of ESRD, if it occurs (rarely happens) Eosinophiluria is not found in AIN due to NSAl Ds. Urine osmolality and urine sodium are useless in thediagnosis of AIN. Papillary necrosis It is ischemic necrosis of the renal papilla, which is usuallybilateral The precipitating factors are DM, Sickle cell disease, chronicalcoholism, and Chronic urinary tract obstruction) Figure 2: IVP showing Ring shadow Clinical features: Consider a diagnosis of papillary necrosis if a suddendeterioration of KFT in a patient who uses NSAl Ds and has aprecipitating factor. Fever, Hematuria, Flank pain Acute renal failure with oliguria or anuria If chronic urinary tract obstruction, asymptomatic sloughingof the pyramid, and necrotic tissue are present in the urine Page 117 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diagnosis: Sudden deterioration of KFT in a patient with DM or chronic urinary tract obstruction Necrotic tissue in urinalysis IVP (intravenous pyelography): ring shadow CT scan is the most accurate test Clinically, Papillary necrosis is very similar to pyelonephritis Treatment: Supportive treatment of acute renal failure Treatment of the underlying cause Analaesic nephropathy Prostaglandin causes afferent arteriole dilation, so NSAl Ds inhibit prostaglandin and result in renal vascular insufficiency High-dose analgesia can cause ATN, AIN, Membranous glomerulonephritis, or Vascular insufficiency (Papillary necrosis) Renal impairment with a history of NSAl Ds use and the absence of other possible causes is diagnostic (diagnosis of exclusion) Treatment: stop the offensive medication and supportive measures Summary of tub UIar diseases: They are generally acute Caused by toxins (drugs, hemoglobin, myoglobin, urate) None of them cause Nephrotic syndrome or massive proteinuria A biopsy is not needed for diagnosis They are not treated with steroids Immunosuppressive drugs are not used for treatment Removing the toxin and correcting hypoperfusion is the only treatment Table 6: Summary of Tubular diseases Page 118 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Post-renal acute renal failure It is a deterioration of renal function due to obstruction ofthe urinary tract History of previous urinary symptoms (hematuria, renal colic,etc. ) Anuria is a common feature of post-renal obstruction Diagnosis: BUN/Cr 20:1 Antegrade or retrograde pyelography Cystoscopy HRCT Treatment: Relieve the obstruction Introduction to the glomerular diseases A group of inflammatory disease that affects the glomerulusof both kidneys They are generally chronic, not caused by toxins orhypoperfusion, and often treated by steroids and immunosuppressants Renal biopsy is the most accurate test Primary glomerular diseases Secondary glomerular diseases Minimal change disease SLE, DM Membranous Sarcoidosis glomerulonephritis Amyloidosis Membranoproliferative Polyarteritis nodosaglomerulonephritis Henoch Schönleinlg A nephropathy purpura (HSP)Goodpasture syndrome Malarial nephropathy Focal segmental HUS glomerulosclerosis Granulomatosis with pol an iitis Table 7: Primary and secondary glomerular diseases Page 119 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Pathogenesis: There are two main processes: Circulating immune complex deposition o Viruses (HBV, HCV, EBV, HIV, Measles, Mumps) Bacteria (group A beta-hemolytic streptococci, streptococcus Viridians, staph., salmonella, Gonococci) o Parasites (Plasmodium malaria, filariasis, Schistosomiasis) o Drugs (penicillamine) o Host antigen (DNA in SLE, malignant tumors) Anti-GBM antibodies 5% (Goodpasture syndrome) Clinical presentations of glomerular diseases Sub-nephrotic proteinuria Selective proteinuria: Glomerular injury only allows the passage of albumin, but not larger molecules like globulin Non-Selective proteinuria: when Glomerular injury allows the passage of albumin and the larger molecules like globulin Nephrotic syndrome It results from glomerular damage that allows the passage of more protein to the urine (proteinuria > 3. 5 grams/day) Clinical features and pathogenesis: Hypoalbuminemia: o Occurs due to protein loss in the urine o This will result in reduced oncotic pressure and anasarca (started as puffiness around the eyes) Hypercholesterolemia: while the liver tries to compensate for the low protein levels, it will produce cholesterol. Decreased renal perfusion due to decreased plasma volume —+ activation of the renin-angiotensin system sodium water retention Increased risk of infection (due to immunity proteins loss) Hypercoagulability occurs due to: o Loss of anti-thrombin Ill in urine o Altered levels of protein C and S o Hyperfibrinogenemia (increased hepatic secretion) o Increased platelet tendency to aggregate Page 120 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Examples of nephrotic diseases: Minimal change disease Membranous glomerulonephritis Focal segmental glomerulosclerosis Amyloidosis Diabetic nephropathy Drugs (penicillamine, Gold, Mercury, cadmium) Allergic reaction General treatment: Loop diuretics and a low salt diet for edema. HMG-COA reductase inhibitors for dyslipidemia Anticoagulation to treat and prevent thrombosis Maintain blood pressure and electrolytes within normal Albumin infusion with mannitol can induce dieresis in ofiguric renal failure Specific treatments (steroids and immunosuppressants) Nephritic syndrome It is also known as glomerulonephritis The glomerular damage will lead to the passage of RBCs, The inflammatory process and local edema of the nephron lead to decreased GFR, less proteinuria, and azotemia. Clinical features and pathogenesis: Proteinuria < 3. 5 grams /day Hypoalbuminemia and edema (more in nephrotic) Hematuria with dysmorphic RBCs and RBC casts More renin-angiotensin system activation leads to HTN Renal dysfunction and azotemia Figure 3: RBC cast in urine consistent with glomerulonephritis Page 121 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Examples of nephritic diseases: Anti-GBM antibody disease Granulomatosis with polyangiitis Microscopic polyangiitis Henoch-Schönlein purpura lg A nephropathy Alport syndrome Diseases that cause both nephritic and nephrotic: Diffuse proliferative GN Membranoprofiferative GN Post-streptococcal GN Rapidly progressive glomerulonephritis RPGN is a clinical syndrome characterized by glomerulonephritis with progression to renal failure within weeks. Severe damage to the glomerulus allows the larger molecules (fibrin) to pass through the glomerulus Fibrin activates the cellular proliferation with macrophage migration and the formation of a crescent of Bowman's capsule. Patient end with impaired filtration through the glomerulus, which lead to uremic syndrome Nephritic/nephrotic syndrome The presence of mixed features between nephrotic and nephritic syndromes Causes: Diffuse proliferative glomerulonephritis Membranoproliferative glomerulonephritis Page 122 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Disorders of nephrotic syndrome Diabetic nephropathy: The most common cause of secondary nephrotic syndromes Annual screening of albumin creatinine ratio (ACR) isindicated for all diabetic patients Screening should be started at the time of diagnosis for type2 DM but after 5 years in Type I DM. Diabetic nephropathy is diagnosed clinically without theneed for a routine biopsy. The treatment of choice is ACE inhibitors or ARBs to protectthe nephrons from further damage. Minimal change disease: The most common cause of primary Nephrotic syndrome inchildren (10% of nephrotic diseases in adults)The biopsy will be normal under the light microscope but willshow effacement of the foot processes of the podocytesunder the electronic microscope. It is the most nephrotic disorder to respond to steroids The specific treatment: prednisolone (60mg/day) for 8weeks. However, if the disease is resistant to steroids, usecyclophosphamide 3mg/kg for 6 — 8 weeks. Membranous glomerulonephritis: The most common cause of primary Nephrotic syndrome inwhite adults (40's to 50's age group) Secondary causes include (HBV, HCV, malaria, lymphoma,SLE, NSAl Ds, etc. ) High rate of renal vein thrombosis and coagulopathy. 50% associated with colon, lung, or stomach cancer The fate: o One-third: spontaneously recovered within 12 monthso One-third will progress to ESRDo One-third: remain proteinuric Treatment: o Treat the concomitant HBV infectiono Steroids, azathioprine, chlorambucil, cyclosporine, cyclophosphamide, or cytotoxic agents for 6 months Focal segmental glomerulosclerosis: It is the most common cause of nephrotic syndrome inblacks, intravenous drug users, and HIV patients. Treatment with prednisolone is the most appropriate Cytotoxic agents are used for refractory cases Page 123 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Disorders of nephritic syndrome Post-streptococcal Glomerulonephritis PSGN results from a post-infectious complication of Group-A beta-hemolytic streptococci (Streptococcus pyogenes) of the throat or skin. The resulting immune complexes will lead to glomerular injury Post-streptococcal GN usually follows infection by I —3 weeks Clinical features: Picture of nephritic syndrome (hematuria with RBC casts, oliguria, HTN, high urea and creatinine, low CFR) Low complement C3 and C4 but returns to normal after 12 weeks Positive ASO titer Biopsy: (best) electron microscopy shows subepithelial HUMPS caused by lumpy immune complex deposits Treatment: Bed rest, Low salt diet Treatment as AKI, if present Diuretics to reduce HTN and edema Antihypertensive medications may be required Antibiotics, if the culture is positive Causes of glomerular diseases with low complement levels: Post-streptococcal glomerulonephritis Subacure bacterial endocarditis Membranoproliferative glomeruloneprhritis Cryo lobulinemia Page 124 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Ig A Nephropathy Also called Berger's disease or mesangioproliferative glomerulonephritis It is the most common cause of glomerulonephritis worldwide Occur due to lg A deposition in the glomerulus Gross Hematuria 1-2 days after an upper respiratory infection Clinical features: Picture of nephritic syndrome (hematuria with RBC casts,HTN, high urea and creatinine, low CFR) Nephrotic range proteinuria is rare (worse prognosis)Normal complements Serum lg A elevated in 50% of cases Histology shows mesangial hypercellularity, positiveimmunofluorescence for lg A & C3 Treatment: No treatment, usually spontaneous resolution If it progresses to ESRD, a renal transplant is indicated If severe proteinuria, ACEI and steroids are the treatment. Prognosis 25% of patients develop ESRF Markers of a good prognosis: frank hematuria Markers of poor prognosis: male gender, more proteinuria,HTN, hyperiipidemia Timing affer URTI main symptom C3 and C4 Biopsy Ig A nephropathy PSGN I —2 days I —2 weeks Hematuria Proteinuria Normal Low Mesangial Lumpy subepithelial hypercellularity immune complex deposits Table 8: PSGN vs. lg A nephropathy Page 125 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Goodpasture syndrome Goodpastu-re syn&orre is a cfricd that corrv Ées $nerüoneptvifis and hemarhoge d..ee to ir*-ry medated by Anf-glorrea. ÀŒ baserrerrt rrerrbcone anfitxxfy (Anî-GBM) Hemopty* and hernatuia Œe tt-e man ieaft-xes but no upper re$*ata-y invdvement Sgns ared syrrptorm of VŒcuüt É Œe t JS. ya%y beca-se the &seŒe irrited to Ùng and Edneys C"cd Us.-dy hvotves ages 5 40 yeŒs cnd rrxe c05r tmocn The orset of tte may be preceded 60E of CŒ— Hernopty± pcecedes foc weeks to rnoatt-s, a-. d it É asociated dyspaea vittl feaiuxes of rcpidy pcoges Sve Cû±d picture wggesfive of the CBC anerria (ctvoric Hood Zs) CXR st-. c..s baaterd frtfltrafion TLco to pc. frnonay hemochcge) Ani-GBM deiecfion in serurn (best tatl Rer'd 50psy shc. à'eg EneŒ oa GBM-the mŒi acaxate taf-Steroi& Cydophosphœride can be helpfd to remove Anfi-GBM ? cge | INTERNAL1-17AFEEF-MERGED-1.pdf |
Granulomatosis with polyangiitis Granulomatosis with polyangiitis was previously called Wegener's granulomatosis It is a vasculitis of the upper and lower respiratory tract alongwith glomerulonephritis leading to necrotizing inflammationof the glomerulus, nasopharynxe and lungs Clinical features: Systemic non-specific symptoms (fever, weight loss)Respiratory symptoms: o Features of sinusitis, nasal septal perforation, andsaddle nose deformity o Cough, hemoptysis, dyspnea, Chest X-Ray: cavitarylesion Renal features: hematuria, proteinuria Eye: conjunctivitis, scleritis, Episcleritis Skin: rash, ulcers, nodules Look for upper and lower respiratory involvement with renal insufficiency Diagnosis: Suggestive history of Wegener's granulomatosis High ESR Positive serology for ANCA (c ANCA 90% and p ANCA 10%)Chest x-ray: a wide variety of presentations, includingcavitating lesions Renal biopsy: crescentic glomerulonephritis Treatment: Steroids, Cyclophosphamide c ANCA: cytoplasmic antineutrophil cytoplasmic antibody Wegener's granulomatosis p ANCA: perinuclear antineutrophil cytoplasmic antibody Churg-Strauss syndrome Microscopic polyangiitis Table 9: CANCA vs. p ANCA Page 127 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Churg-Strauss syndrome Also known as Eosinophilic granulomatosis with polyangiitis It is an ANCA-associated pulmonary-renal syndrome It is associated with Asthma and Eosinophilia Paranasal sinusitis, mononeuritis multiplex may present p ANCA positive in 60% Treatment: steroid Henoch Schönlein purpura (HSP) HSP is a type of small vessel vasculitis of unknown cause It is also known as lg A vasculitis More common in male children Clinical features: Gl: Abdominal pain, melena Skin: Palpable purpura, usually in lower limbs and buttocks Joints: Arthralgia Renal: Nephritic syndrome and renal insufficiency Figure 4: A characteristic rash of HSP Diagnosis: Mainly clinical diagnosis Biopsy is the most accurate test (leukocytoclastic vasculitis) Treatment: Supportive treatment Usually, Full recovery within several weeks Steroids are effective in reducing tissue edema, arthralgias, and abdominal discomfort Page 128 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Alport's syndrome It is an x-linked inherited condition that leads to a congenital collagen defect Symptoms: Progressive renal failure (glomerular disease) Hematuria Sensorineural deafness Visual disturbances (loss of collagen fibers in the lens of theeye) Look for a patient with deafness and renal impairment and has a family history of the same condition in his mother or maternal uncle. Treatment: No Cure ACE inhibitors can slow the progression of the renal disease SLE nephritis SLE can give any degree of renal involvement Class IV is the most common and severe form of SLE nephritis Biopsy is the most accurate test Class I Class Il Class Ill Class IV Class V Class VINormal kidney Mesangial glomerulonephritis Focal (and segmental) proliferative glomerulonephritis Diffuse proliferative glomerulonephritis (most common and most severe form) Diffuse membranous glomerulonephritis Sclerosing glomerulonephritis Table 10: WHO classification for lupus nephritis Treatment: Treatment based on stage according to biopsy Mild inflammatory changes may respond to steroids Severe proliferative disease is treated with steroids combined with cyclophosphamide and mycophenolate. Page 129 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Amyloidosis Amyloidosis is an abnormal protein deposition In primary amyloidosis, the source of protein is unknown, and the kidneys are the main target of the protein deposition Causes: Idiopathic (primary amyloidosis) Myeloma Chronic inflammatory diseases: o Rheumatoid arthritis o Inflammatory bowel disease o Chronic infections Diagnosis: Biopsy showing green birefringence with Congo red staining is the most accurate test. Treatment: Treatment of the underlying disease Melphalan and prednisolone (for primary or unsuccessful treatment) Chronic Kidney disease (CKD) It is an irreversible deterioration of the renal function that persists for more than 3 months This will lead to excretory, metabolic, and endocrine dysfunction of kidneys, and the clinical syndrome of uremia The leading cause of death in CKD patients is cardiovascular disease. Causes: Diabetic and HTN nephropathy are the most common causes Glomerular diseases Tubulointerstitial diseases Renovasculad diseases (vasculitis) Structural diseases (e. g., PKD) Page 130 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Stages of CKD: Stage Stage I Stage Il Stage Ill Stage IV Stage VSeverity Mild Mild Moderate Severe ESRDGFR m L/min Normal 60-89 30 59 15-29 < 15Clinical state No symptoms No symptoms Anemia may present Electrolyte disturbances Dialysis dependent Table l: CKD stages according to GFR Clinical picture: Non-specific symptoms: (Nausea, vomiting, pruritus,diarrhea, convulsions, coma) Features of complications (anemia, uremia, etc. )Urinary symptoms: (Oliguria, anuria, nocturia, Polyuria)Renal osteodystrophy Sensory-motor peripheral neuropathy Signs and symptoms of electrolyte disturbance Renal osteodystrophy: Osteitis fibrosa cystica: High PTH (secondary hyperparathyroidism) One year later, x-ray findings of subperiosteal erosions ofterminal phalanges and the lateral end of the clavicle Adynamic bone disease: Chronic illness or aggressive vitamin D treatment willsuppress the PTH Increased risk of fractures Made worse with bisphosphonates Osteomalacia: Vitamin D deficiency Hypocalcemia, bone pains, and fractures Table 12: Types of renal osteodystrophy Treatment: Dietary modifications (protein, and Na+ restriction)Treatment of complications (uremia, HTN, electrolytes)Treatment of anemia (erythropoietin injections, target Hb notmore than 1 1) Calcium replacement, I-alpha Regular dialysis typically 2 — 3 times weekly Renal transplant (definitive treatment) Page 131 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Drug dose adjustments in CKD: Many medications need dose adjustment in CKD to prevent their toxicity and accumulation. Usually, they are adjusted based on the estimated GFR or creatinine clearance but not serum creatinine. Dose adjustment may be a reduction of the dose, lengthening the dosing intervals, or both Loading doses usually do not require an adjustment Indications of dialysis in renal failure Uremic symptoms (pericarditis, encephalopathy, platelet dysfunction, or convulsions) Fluid overload Refractory hyperkalemia > 7 m Eq/l Acidosis PH < 7. 2 Serum creatinine > 10 mg/dl Serum urea > 200 mg/dl Regular hemodialysis for ESRD patients. Table 13: Indications for hemodialysis Acute on top of chronic renal failure: The patient is known to have CKD and presents a new kidney function deterioration (elevation of the baseiine creatinine). The acute deterioration can be reversible to the baseline with proper management. However, diagnosis and treatment are just like that in acute renal failure, and then to manage the patient as History CBC Renal U/S Baseline creatinine CKD according to its stage. Table 74: Acute on top of chronic renal failure Acute renal failure Previously normal KFT Not informative Normal size kidney Normal baseline Chronic renal disease History of abnormal KFT History of any cause of CKD Anemia of chronic disease Small size kidneys except in DM, hydronephrosis, Amyloidosis, Multiple Myeloma, and PKD. High baseline Table 15: Acute vs. Chronic renal failure Page 132 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Cystic diseases of the kidney Characterized by epithelium-lined cavities filled with fluid or semisolid debris within the kidneys, they include: Simple cysts Medullary cystic kidney Medullary sponge kidney Autosomal dominant polycystic kidney diseases (ADPKD)Autosomal recessive polycystic kidney diseases (ARPKD) Acquired cystic kidney disease (in chronic hemodialysis patients) Simple renal cyst it is the most common renal cystic disease At least 50% of the population over 50-year-old have a cyst Usually asymptomatic and diagnosed during an ultrasound that is done for another purpose Imaging used are CT scan, renal ultrasound, urography, or angiography) In the absence of infection or suspected malignancy, there is no need to treat simple renal cysts Adult polycystic kidney diseases (ADPKD) PKDs are genetic diseases in which kidneys are filled with hundreds of cysts; kidneys become larger than normal and lose function over time Adult PKD is an autosomal dominant, while infant PKD is an autosimal recessive These cysts are lined by tubular epithelium Two types of gene mutations in ADPKD o PKDI (more severe and early onset) (code for polycystin 1 ) o PKD2 (less severe and later onset) (code for polycystin2) Page 133 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Clinical features: Flank pain, abdominal pain, abdominal mass HTN (due to compression on blood vessels and activation of RAS) Kidney stones (due to compression on collecting ducts and urinary stasis) Hematuria Renal insufficiency and renal failure (manifest in adulthood) ADPKD is associated with cyst formation In other body parts: Liver cysts (most common site outside kidneys) Seminal vesicle cysts Pancreatic Cysts Aortic root dilatation, aortic dissection Mitral valve prolapse, Tricuspid incontinence Berry aneurysm (risk of Subarachnoid hemorrhage) Treatment: ACEI/ARB for treatment of HTN Dialysis, or renal transplant in case of ESRD Ursodiol for treatment of cholestasis Treatment of portal HTN Autosomal recessive PKD is caused by a mutation in the PKHDI gene that codes for fibrocystin protein. It is characterized by oligohydramnios in-utero and early ESRD. Prenatal ultrasound will show the oligohydramnios and the cystic kidney. Page 134 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Electrolyte disturbances Hypernatremia Normal serum sodium is 135 — 145 m Eq/l Hypernatremia is defined as serum Na > 145 m Eq/l Occur when there is a loss of free water Causes include (6D's) Diuresis, Dehydration, DI, Doctors (iatrogenic), Diarrhea, and Disease of kidney Clinical features: Thirst, Dry tongue Weakness, Restlessness Convulsions Changes in the level of consciousness (up to coma) Treatment: Treatment of the cause Correction rate s 0. 5 m Eq/l/h (to prevent brain edema) Fluid replacement: o For hypovolemic patients, start with isotonic 0. 9% Na Cl to correct the water deficit o If euvolemic and asymptomatic, start D5W, 0. 45% Na Cl, or enteral fluid o For hypervolemic hypernatremia (rare), use D5W and diuretics. Water deficit calculation: Free water deficit = TBW * ([Na/1401 1) TBW = 0. 5 * weight (for female), 0. 6 * weight (for male) Table 16: Water deficit calculation Page 135 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hyponatremia Hyponatremia is defined as serum Na < 135 m Eq/l There are 3 patterns of hyponatremia according to fluid status in the body Hypervolemic hypotonic hyponatremia: Hyponatremia with increased extracellular fluid Seen in edema-associated conditions (Congestive heart failure, liver cirrhosis, Nephrotic syndrome, advanced renal failure). Pathogenesis: water retention leads to dilutional hyponatremia Treatment: o Water restriction o Diuretics (i. e., loop diuretics) o Hemodialysis in resistant cases Hypovolemic hypotonic hyponatremia: Hyponatremia with decreased extracellular volume Causes: diarrhea, vomiting, dehydration, diuresis, nephropathy, adrenal insufficiency, burns, sweating, fever... (These causes also may cause hypernatremia) Euvolemic hypotonic hyponatremia: Hyponatremia with normal extracellular fluid Causes: (pseudo-hyponatremia, SIADH, Addison's disease, hypothyroidism, psychogenic Polydipsia) In SIADH: o Due to high ADH, the urine is inappropriately concentrated (high urine osmotafity) o High urine sodium, but uric acid and BUN are low o High serum ADH (the most accurate test) In pseudohyponatremia: o Hyperglycemia —+ increased serum osmolarity free water shifted to intravascular space-+ drop in sodium level. o Each 100 mg of glucose above the normal level reduces I. 6 m Eq in serum sodium o No treatment for pseudo-hyponatremia (only correct the glucose level) Page 136 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Thyroid hormone is needed to excrete water; so, in hypothyroidism, water excretion is decreased, leading to hyponatremia Clinical features of hyponatremia: Present with CNS problems (Confusion, lethargy, disorientation, seizures, coma) Symptoms of hyponatremia depend on how fast it occurs (the more acute the hyponatremia, the more severe the symptoms) Treatment of hyponatremia: The correction rate should not exceed 8 — 10 m Eq/l every day to avoid osmotic demyelination syndrome Asymptomatic: restrict fluids Moderate symptoms (minimal confusion): saline and loop diuretics Severe (coma): hypertonic saline is indicated Demeclocycline and fludrocortisone may be used (block the action of ADH) Sodium deficit calculation: Sodium deficit = TBW * (desired sodium — serum sodium) TBW = 0. 5 * weight (for female), 0. 6 * weight (for male) Table 17: Sodium deficit calculation The composition of common IV fluids: Normal saline Y2 saline 1/4 saline 3% saline Ringer's lactate154 m Eq 77 m Eq 39 m Eq 512 m Eq 109 m Eq Na K Ca 154 m Eq 77 m Eq 39 m Eq 512 rn Eq 130 m Eq 4 m Eq 3m Eq 28 m Eq Table 18: common IV fluids and their compositions per liter Page 137 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hyperkalemia It is defined as the serum potassium of more than 5. 3 m Eq/I It is a life-threatening condition that may result in a fatal arrhythmia If the lab result came with hyperkalemia: The most urgent step is ECG (to rule out arrhythmias) The first step is to repeat the test with a new sample to rule out pseudohyperkalemia. Causes of pseudohyperkalemia: Hemolyzed sample Delay in sample analysis Tourniquet use when drawing sample Extreme leukocytosis or thrombocytosis Causes of true hyperkalemia Oliguric renal failure Drugs (Potassiurn-sparing diuretics, ACE-I/ARB, NSAl Ds, cyclosporine, heparin, Beta-blocker, digoxin) Type IV RTA Addison's disease Shifting potassium out of cells: o Acidosis o Rhabdomyolysis o After chemotherapy (tumor lysis syndrome) o Insulin deficiency Clinical features: Cardiac conduction abnormalities on ECG Low or absent P, Prolonged PR, Wide QRS, peaked T wave Sine wave (severe hyperkalemia) Cardiac arrhythmias Figure 5: ECG changes in Hyperkalemia Neuromuscular effect: muscular weakness, flaccid muscle paralysis, paresthesia of the face, tongue, feet, and hands Gl: Nausea, Intestinal colic, and diarrhea (in very high levels of potassium) Page 138 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Treatment (Anti-hyperkalemia protocol): Effect Agent Membrane Calcium stabilization gluconate Shifters Excretors Definitive Insulin SABA Furosemide Na HC03 Kayexalate Hemodialysis Dose 10 m L, over 10 minutes 10 u in 50 m L of 50% dextrose 20 mg nebulized 40 — 80 mg 150 mmol/L 15-30g Onset Immediate 20 minutes 30 minutes 15 minutes Hours > 2 hours Immediate Table 19: anti-hyperkalemia protocol Calcium gluconate: It stabifizes the cell membrane but does not reduce the serum potassium level It is indicated if there are ECG changes or the serum potassium is 7m Eq/L To avoid acute hypercalcemia, provide calcium gluconate with 100 m L of D5%W infusion over 20 —30 minutes Hypercalcemia potentiates the cardiac toxicity of digoxin; hence, it is better to avoid calcium gluconate in digoxin users Other notes: Cardiac monitoring is the most important in hyperkalemia. Sodium bicarbonate is indicated in hyperkalemia in the presence of acidosis Hemodialysis is indicated in refractory hyperkalemia of more than 7 m Eq/L Kayexalate "sodium polystyrene sulfate" and Calcium resonium "calcium polystyrene sulfate" remove potassium from the Gl tract Hyperkalerria and hypokalemia do not cause seizures; hypernatremia causes CNS symptoms, while hyperkalemia causes muscular and cardiac symptoms Page 139 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hypokalemia It is defined as the serum potassium of less than 3. 5 m Eq/I Causes: Intracellular shift: Alkalosis, High insulin, Beta-agonist, Barium intoxication Renal loss: diuretics, RTA type I and Il, primary hyperaldosteronism, Cushing's syndrome, Barter's syndrome, and hypomagnesemia Gl loss: vomiting, diarrhea, Ileostomy, ureterosigmoidostomy Poor intake Clinical features: Fatigue, weakness, cramps, paralysis, anorexia, nausea, vomiting Decreased bowel mobility (ileus) Hyperglycemia: due to suppressed insulin Restless legs Rhabdomyolysis Arrhythmias Hypotension (due to decreased peripheral resistance) ECG changes: (high P wave, Depressed ST, broad flat T wave, U wave) Metabolic alkalosis Treatment: Potassium-rich diet (Banana, orange, tomato, potato, milk) Potassium supplement (oral or IV according to the case) Correct hypomagnesemia There are magnesium-dependent potassium channels that open and spell potassium in urine in case of hypomagnesemia Kdenc Jt = (Knormal bwerltmit ¯ Kmeasured) X Bodyweight X 0. 4 Page 140 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hypomagnesemia Hypomagnesemia is defined as serum Mg level < 1. 5 m Eq/l Causes: Decreased Mg intake (malnutrition, malabsorption) Increased Mg loss (diuretics, diarrhea, vomiting, alcoholism) Others: DKA, pancreatitis Clinical features: Hyperactive reflexes Concurrent hypocalcemia: Tetany, Paresthesia, Irritabifity, seizures Concurrent hypokalemia: Arrhythmias ECG: long PR and long QT intervals Treatment: IV or oral supplementation Hypokalemia and hypocalcemia will not correct until Mg corrected Inherited defects of the nephron Renal tubular acidosis (RTA) Increased acidity of blood due to an impaired renal ability to maintain acid-base balance All types of renal tubular acidosis (RTA) are associated with hyperchloremic metabolic acidosis with a normal anion gap Types of RTA: Type I RTA (Distal classic type): Failure of distal tubules to secrete ions and reabsorb HCOs Type Il RTA (proximal type): Failure of sodium bicarbonate reabsorption in proximal tubules Type IV RTA: (hyporeninemic hypoaldosteronism) o It is the most common type of RTA o Reduced aldosterone leads to sodium loss and retention of potassium and H+. Page 141 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Type Potassium Urine anion gap Type I Hypokalemia Positive Type Il Hypokalemia Normal or negative Type IV Hyperkalemia Positive Urine p H > 5. 5 < 5. 5 < 5. 5 Table 20: Laboratory features of RTA types Causes of RTA: Type l: SLE, RA, Sjögren's syndrome, amphotericin B Type Il: Wilson disease, Fanconi syndrome, tetracycline Type IV: hypoaldosteronism, diabetes Diagnostic tests: Type l: Urine PH still > 5. 5 after ammonium chloride infusion Type Il: Urine PH will rise after bicarbonate is given Type IV: Persistent high urine sodium despite low sodium diet Common complications of RTA: Type l: Nephrocalcinosis, calcium oxalate renal stones. Type Il: Osteomalacia Type IV: hyperkalemia Treatment of RTA: Type l: o Always correct potassium before acidemia o Sodium bicarbonate Type Il: o Bicarbonate (will not correct the acidemia alone) o Thiaide diuretics (induces hypovolemia and reduce the GFR leading to reduced bicarb loss) o Potassium-sparing diuretics (will limit potassium loss) Type IV: o Correction of hyperkalemia o Fludrocortisone and sodium bicarbonate 85 90% of bicarbonates are normally reabsorbed in proximal tubules, so it is easier to control type I RTA than type Il RTA Page 142 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Fanconi syndrome It is a defect in proximal convoluted tubules This will result in the loss of the following substances in the urine: Glucose loss glucosuria Phosphates loss-4 phosphaturia Amino acids loss-+ aminoaciduria Bicarbonate loss-+ metabolic acidosis Water loss-+ dehydration Potassium loss —+ hypokalemia Sodium loss-+ hyponatremia Barter, Gitelman, and Liddle syndromes Barter syndrome Hypotension Hypokalemia Hypocalcemia Hypercalciuria Normal Mg Gitelman syndrome Liddle syndrome Hypotension Hypertension Hypokalemia Hypokalemia Hypercalcemia Hypernatremia Hypocalciuria Hypoaldosteronism Hypomagnesemia All are autosomal recessive disorders All result in metabolic alkalosis Bartter syndrome: Salt loss in the thick ascending loop of Henle Gitelman syndrome: Defect in thiazide-sensitive sodium-chloride symporter in the distal convoluted tubules Liddle syndrome: Sodium reabsorption with potassium loss Table 2 J: Genetic syndromes that affect the renal tubules Page 143 | INTERNAL1-17AFEEF-MERGED-1.pdf |
HTN HTN is defined as BP 140/90 It classified as (Essential '95%" vs. Secondary "5 %") It is usually asymptomatic but could present as headaches or the symptoms of its cause. Causes of secondary HTN: Renal artery stenosis Chronic kidney disease, glomerulonephritis OSA (obstructive sleep apnea) Hormonal (pheochromocytoma, Cushing's, hyperaldosteronism, hyperparathyroidism) Liddle syndrome. Normal BP < 120/80: If the cuff is small, there will be a false high reading If the cuff is large, there will be a false low reading Stages of elevated blood pressure: Pre-hypertension (120-139/80-89) — "this is not a disease; it is a risk category" stage 1 (140-159/90-99) stage 2 (2160/100) Other types: White-coat HTN: high readings at the clinic but normal at home (need Home Blood Pressure Monitoring — HBPM) Masked HTN: high readings at home but normal at the clinic HTN urgency: severe HTN without end-organ damage HTN emergency: severe HTN with end-organ damage Emergency HTN: HTN encephalopathy Intracranial hemorrhage ACS, LV failure Acute aortic dissection Eclampsia Risk factors: Family history, smoking, CKD, high Salt/Sodium diet, obesity, increasing age, male sex, and sedentary lifestyle. Diagnosis: (one of the following is diagnostic) Two separate readings, or Very high reading 2 180 systole, or Emergency/Urgency HTN page 144 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Renal artery stenosis: The most common cause in elderly is atherosclerosis, The most common cause in young patients is fibromuscular dysplasia Suspect if deteriorating renal function (> 30% increase in creatinine) in a patient with HTN and newly put on ACEI/ARB Diagnosis: abdominal bruit (O/E), Doppler UIS, angiography (best) Treatment: angioplasty with stenting ACE! is contraindicated in bilateral disease (they lead to an increase in creatinine) Table 22: Important points about renal artery stenosis Approach for treatment of HTN:-The first step is to Exclude secondary causes (and treat the cause if present) If there is no secondary case, treat it as essential HTN: o Try lifestyle modifications initially o Anti-HTN medications if there is no improvement by lifestyle modifications If stage I — start treatment with one drug If stage 2 — start treatment with 2 drugs, one of them is diuretics Associated condition The drug of choice HTN + DM ACEI or ARBs HTN + BPH Alpha blockers HTN + CAD Beta-blockers and CCBs HTN in pregnancy Methyldopa, labetalol, Hydralaine Table 23: The drug of choice for HTN in specific groups Page 145 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Is the patient old or black? ACEI / ARB CCB ACEi or ARB + CO ACEi or ARB + CCB + thiazide-like diuretics Is serum K > 4. 5?< Step 1 < Step 2 < Step 3 < Step 4 Add Aldactone Increase Thiazide like diuretics dose Target blood pressure Target for 60 years patients: < 150/90 mm Hg Target for < 60 years patients: < 140/90 mm Hg DM or CKD : < 140/90 mm Hg regardeless of the age Figure 6: Treatment approach for HTN Important notes about HTN: In urgency HTN, do not decrease BP rapidly (increase the risk of brain edema, and do not use diuretics) Complications of HTN include: Retinopathy, Nephropathy, Encephalopathy, Brain Hemorrhage. and LV failure Serum creatinine should be monitored after administration of ACEI; if it is increasing by more than 30% stop ACEI and investigate for renal artery stenosis Refractory HTN is an uncontrolled HTN despite treatment with 3 drugs in the maximum dose, one of which is a diuretic. It may be caused by: o Non-compliance with medications o Non-compliance with a low salt diet o Secondary cause of HTN Page 146 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Endocrinology CHAPTER 2 AM JAD K. ALAFEEF Phone number: +962798843824 E-mail: Afeeef. 2005@gmail. com Page 147 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Introduction to the Endocrinology Hormone Counterregulation It is a hormone that opposes the action of another. Glucose Counter-regulation: The action of insulin is counter-regulated by glucagon, epinephrine (adrenaline), norepinephrine (noradrenaline), cortisol, and growth hormone These counterregulatory hormones raise the level of glucose in the blood by promoting glycogenolysis, gluconeogenesis, ketogenesis, and other catabolic processes. For example, the exercise-induced reduction in blood glucose cause increases in levels of epinephrine, norepinephrine, cortisol, and growth hormone. This will lead to the maintenance of adequate blood glucose for muscle uptake Blood Pressure Counter-regulation: The natriuretic peptide (BNP) counter-regulate against renin, angiotensin, and aldosterone, which elevate the blood pressure. Hormonal feedback regulatory systems The hormonal positive and negative feedback are fundamental in the endocrine system. The examples of the negative feedback are numerous; the high T4 and T3 will suppress the TSH and TRH secretion. Another example is when the high cortisol levels will suppress the ACTH release from the pituitary gland. Child feeding stimulates milk production, which causes further feeding is an example of positive feedback. Page 148 | INTERNAL1-17AFEEF-MERGED-1.pdf |
TSH Pituitary gland Negative feedback T3 and T4 Thydoid gland Figure 7: Example of the negative feedback The pituitary gland Basics of the pituitary gland The pituitary gland is an endocrine gland located in Sella turcica It is the master gland of the body because it is the most important gland in the endocrine system. It contains two lobes: anterior and posterior The anterior pituitary gland secretes the following: o Growth hormone (GH) o Luteinizing hormone (LH) o Folficular stimulating hormone (FSH) o Thyroid-stimulating hormone (TSH) o Adrenocorticotropic hormone (ACTH) o Prolactin (PRI) Posterior pituitary stores and releases the following hypothalamus hormones: (storage function) o Oxytocin o Antidiuretic hormone (ADH) Page 149 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Basics of the pituitary tumors Pituitary tumors are usually benign (adenomas); primary malignancy is rare Clinical features: Compression effect of the tumors: o Visual field defect: (bitemporal hemianopia or upper temporal quadrantanopia): due to compression on the optic chiasma o Lateral extension to cavernous sinus leads to cranial nerves 3, 4 & 6 dysfunction o Compression of normal tissue of the pituitary gland leads to hyposecretion of the gland hormones. Secretory effects of the tumors: o Gigantism or Acromegaly (excessive GH secretion) o Cushing's disease (with high ACTH) o Hyperprolactinemia Some adenomas are called non-functioning adenomas (no excessive hormone secretion but can cause compression effect) Diagnosis: Clinical features (compression or secretory effects) X-ray skull (lateral view) will show enlarged Sella turcica Pituitary function test MRI of the pituitary gland for localization Page 150 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Acromegaly Acromegaly is a Disease of adult life, characterized by the growth of bulk but not in the height of bone due to over-secretion of GH after puberty Gigantism is a GH oversecretion that occurs before puberty; it increases the bulk and height of the bone. Causes: Pituitary adenoma (Most common cause-usually Macroadenoma) May present as a part of MEN type I Ectopic GH or GHRH production from lymphoma or bronchial carcinoid. Clinical features: Effects of adenoma (headache, vomiting, visual field defect. cranial nerves palsy, hypothyroidism, impotence, amenorrhea) Skeletal changes: o Large hands and feet o Prognathism (large protruding jaw), Large spacing teeth o Prominent supraorbital ridges and large frontal sinus o Spinal stenosis (due to overgrowing vertebral bones) o Increased risk of carpal tunnel syndrome, and OSA Metabolic effects: o Glucose intolerance (effect of insulin-tike growth factor) o DM may present in o HTN o Weight gain Other effects: o Hypogonadism (compression effect and hyperprolactinemia are the main mechanisms) o Colonic polyps and skin tags o Bad body smell (enlarged sweat glands) o Deep voice Diagnosis: Clinical features and the morphology of the patient Fasting serum Insulin-like Growth factor (IGF-I) (the best initial test) GH level 1 hour after ingestion of 70 g glucose (Glucose suppression test) (most accurate test) Page 151 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Fasting serum PRL elevated in 30% (in GH-secreting adenoma, PRL is co-secreted from the adenoma) Pituitary function test (some hormones may be deficient due to compression effect) CT, MRI of the pituitary gland (to localize the adenoma) Treatment: Surgical treatment (Transsphenoidal resection): o It is the initial treatment for most patients o indicated if the surgical cure is likely or CNS pressure effects are present. o Larger adenomas are harder to cure Medical: o Somatostatin analogues (Octreotide acetate) o GH receptor antagonists (Pegvisomant) o Dopamine agonists (Cabergoline or bromocriptine) Radiotherapy (if not responsive to surgery and medical therapy) The efficacy of the treatment is monitored by GH and IGF-I levels Page 152 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hyperprolactinemia It Is an Increased level of PRL hormone PRL function is to stimulate the production of milk by breasts Physiologically stimulated by stress, lactation, and nipple stimulation and suppressed by dopamine and dopamine agonists Causes: Prolactinoma (the most common cause) Primary hypothyroidism (high TRH will stimulate PRL secretion) Pregnancy (high level but opposed by estrogen) Chronic renal failure, liver cirrhosis PCOS Drugs (OCP, estrogen, TCA, Haldol, metoclopramide, dopanine antagonists, verapamil) Clinical picture: Galactorrhea and hypogonadism Unexplained infertility Secondary amenorrhea, oligomenorrhea, or menorrhagia with infertility In men: decreased libido, impotence, decreased pubic and axillary hair, gynecomastia, but galactorrhea is rare in men. Diagnosis: Plasma PRL level TFT, pregnancy test, KFT, LFT CT, MRI of the pituitary gland (done after confirmation of high PRL and excluding secondary causes) Treatment: Treatment is unnecessary if the patient is asymptomatic and fertility is not desired. Dopamine agonists (cabergoline, bromocriptine): o They are the first line in the treatment of prolactinoma o Tumor shrinkage and PRL normalization are the signs of effective treatment Transsphenoidal surgical removal (Indicated if no response to medical treatment) P age 153 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diabetes insipidus (DI) DI results in insufficient (central) or ineffective (nephrogenic) ADH, leading to high volume water loss in urine Types: Central DI: Any CNS disorder (stroke, tumor, trauma, hypoxia, infection, histiocytosis) impair the production of ADH in the hypothalamus or storage in the posterior pituitary gland. Nephrogenic DI: less common, characterized by loss of ADH effect on collecting ducts, caused by (lithium, demeclocycline, CKD, Hypokalemia, hypercalcemia, pyelonephritis, renal amyloidosis, Sjögren's syndrome) DIDMOD syndrome: is a congenital syndrome characterized by central diabetes insipidus, Diabetes mellitus, Optic atrophy, and deafness. Table 24: Features of DIDMOD syndrome Clinical features: High volume nocturia (first clue of DI) Polyuria, Polydipsia Severe hypernatremia (CNS symptoms are possible) Diagnosis: High serum sodium and osmolality Low urine sodium and osmolality ADH is high in nephrogenic type and low in central type Water deprivation test (best initial test) Desmopressin challenge test (best to differentiate between the DI types) Treatment: Central DI: vasopressin (DDAVP) Nephrogenic DI: o Potassium and calcium correction o Stop lithium, demeclocycline, or any possible cause o If no improvement, use hydrochlorothiazide or NSAl Ds Page 154 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hypopituitarism Deficiency of pituitary hormones due to damage in the pituitary gland If all hormones are deficient, it is termed panhypopituitarism Causes: Compressing pituitary adenoma (the most common cause) Others: tumors, trauma, radiation, infection, infarction, hemochromatosis, sarcoidosis, histiocytosis Clinical features: Depends on which hormone is deficient GH loss: lethargy, muscle weakness, short stature (not obvious in adults) LH, FSH: failure of sex hormone production o Women: no ovulation, no menstruation o Men: no testosterone or sperms, Gynecomastia, Impotence o Both will have: Loss of Cibido, Scanty axillary and pubic hair TSH loss: (symptoms of hypothyroidism) ACTH loss: this leads to a decreased cortisol level o Hypoglycemia, Hypotension, hyponatremia, hyperkatemia, Nausea, and vomiting Prolactin loss: no symptoms in men, but a lactation failure in women after birth. ADH deficiency: central diabetes insipidus Untreated or severe Hypopituitarism may cause a coma Melanocyte-stimulating hormone (MSH) loss will lead to hypopigmentation of the skin Diagnosis: Pituitary function test: Testosterone, ACTH, PRL, FSH, LH, TSH, T3, T4, and GH stimulating test Aldosterone is not affected, so serum potassium will remain normal. Treatment: Treatrnent of the underlying cause Hormone replacement therapy (cortisone, thyroxine, testosterone and estrogen, recombinant human growth hormone) Page 155 | INTERNAL1-17AFEEF-MERGED-1.pdf |
The Thyroid gland It is a part of the endocrine system located in the neck Composed of two lobes and connected by an isthmus Secrets thyroxin, which is responsible for metabolic activity in the body Thyroxin secretion is stimulated by TSH, which secreted by the pituitary gland Hypothyroidism It is defined as an inability of the thyroid gland to maintain the body's requirement of the thyroxin hormone It can be primary or secondary, or tertiary Primary hypothyroidism: (will lead to increased TSH) Hashimoto's thyroiditis (the most common cause) Endemic iodine deficiency Idiopathic Atrophy Radioiodine therapy Congenital agenesis Drug-induced (lithium, amiodarone, anti-thyroid drugs) Secondary hypothyroidism: Pituitary lesion, which leads to TSH and thyroxine deficiency Tartary hypothyroidism: Hypothalamus lesion leads to decreased TRH, TSH, and thyroxin Clinical features: Delayed reflexes (most important bed-side test in hypothyroidism) Generalized weakness Cold intolerance Constipation Menorrhagia but lately amenorrhea Brittle nails and hair Peripheral edema (late) Weight gain with decreased appetite Goiter may be present (the first sign in Hashimoto) Thinning of the outer half of eyebrows In pediatrics (large tongue, umbilical hernia, mental retardation) ECG: sinus bradycardia with low voltage Page 156 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diagnosis: Serum TSH (high in primary but low in secondary) Free TA level (low) Anti-thyroid peroxidase or anti-thyroglobulin antibodies in Hashimoto's thyroiditis Dyslipidemia may present Pituitary CT or MRI if secondary hypothyroidism Subclinical hypothyroidism: Elevation of TSH with normal T4No symptoms of hypothyroidism No need for routine treatment of these cases Treatment: Thyroxine replacement orally Indications for treatment in subclinical hypothyroidism: TSH of more than double the normal Positive anti-thyroid peroxidase (anti-TPO)Pregnant patient Hashimoto's thyroiditis Autoimmune disorder against thyroid gland leading tohypothyroidism It is the most common caose of hypothyroidism It may cause thyroid lymphoma as a complication. 10% of patients with Hashimoto thyroidltis may be antibody negative Clinical features: Usually subclinical for years before becoming clinical Goiter (the first sign) Features of hypothyroidism Diagnosis: Mild hyperthyroidism may present initially, but hypothyroidism is inevitable Thyroid function shows clinical or subclinical hypothyroidism Presence of anti-TPO (anti-thyroid peroxidase) and anti-TG (anti-thyroglobufin) antibodies A biopsy may be needed Treatment: Medical thyroxine replacement Surgical treatment for large goiter or suspicion of lymphoma Page 157 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Myxedema Coma It is a medical emergency caused by hypothyroidism and precipitated by stress Clinical features: Hypothermia, hypoglycemia, and hyponatremia Confusion or coma Treatment: Oxygen, Hydrocortisone, Dextrose water Antibiotics Gradual re-warming by blankets Hyperthyroidism It is an increased activity of the thyroid gland which leads to an excessive amount of thyroxin in the body resulting in a high metabolic rate More common in females Causes: Grave's disease (most common 75%): o Caused by thyroid-stimulating antibodies (autoimmune) Will present with diffuse thyroid enlargement and ophthalmopathy o Pretibial Myxedema, myopathy may be a feature Multi-nodular goiter (Plummer's disease) Autonomously functioning solitary thyroid nodule Thyroiditis (sub-acute or postpartum) Drugs (e. g., amiodarone) (amiodarone can cause both hypo or hyperthyroidism) Maybe secondary to pituitary adenoma (TSH will be high) Clinical features: Nervousness, sweating, tremor, palpitation, tachycardia, and angina Weight loss with increased appetite, Diarrhea, Heat intolerance Pretibial Myxedema Amenorrhea, oligomenorrhea, impotence Goiter, Hyperreflexia, Hyperkinetic movement Eye signs (only seen in Grave's disease): Led retraction, Led lag, Conjunctival injection, Ophthalmoplegia, Exophthalmos Page 158 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diagnosis Graves' disease Subacute thyroiditis Silent thyroiditis Pituitary adenoma Unique features Eye signs and skin manifestations Tender thyroid gland Painless, non-tender thyroid gland High TSH level Table 25: disorders of thyrotoxicosis and their unique features Diagnosis: Low TSH, high T3, High T4 (high TSH level is seen inhyperthyroidism secondary to pituitary adenoma)Grave's disease: o Elevated TSH receptor-stimulating antibodyo Antithyroglobulin and anti-microsomal antibodiesmay be high Radioactive iodine scan (RAIU):o Elevated in Graves' diseaseo Low in (subacute thyroiditis, silent thyroiditis,exogenous thyroxine use) Hypercalcemia, high Alkaline Phosphatase Low Thyroglobulin level is useful in patients with thyrotoxicosiscaused by surreptitious use of thyroid hormone Treatment: Carbimazole (anti-thyroid agent) o It can be used in the second or third trimester ofpregnancy o Less hepatotoxic than PTU Propylthiouracil (PTU) (anti-thyroid agent)o Used in the first trimester of pregnancyo More hepatotoxic than methimazoleo Better to use in thyroid storm Thyroidectomy (surgery) Radioactive iodine ablation Beta-blockers (symptomatic control, decreases theconversion of T4 to T3) Eye signs are treated with steroids or by surgery if not responsive. Page 159 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Thyroid storm A medical emergency of hyperthyroidism, Precipitated by stress, infection, trauma Symptoms: Fever, nausea, vomiting, and diarrhea Arrhythmias, Tachycardia, HTN, Heart failure Coma Treatment: Propranolol: o Block the target organ effect of thyroxine o Block the peripheral conversion of T4 to T3 Propylthiouracil or Methimazole: o PTIJ is preferred over methimazole o Block thyroid hormones production Steroids Radioactive iodine ablation (for a permanent cure) Hypothyroidism Bradycardia Constipation Weight gain with less appetite Fatigue, depression, coma Hyporeflexia Cold intolerance Heat preference Hypothermia Coarse hair, dry skin Hyperthyroidism Tachycardia, arrhythmia, AF Diarrhea Weight loss with more appetite Anxiety, restlessness, nervousness Hyperreflexia Heat intolerance Cold preference Fever fine hair, moist skin Table 26: Hypothyroidism vs. Hyperthyroidism Page 160 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Sub-Acute thyroiditis (De Quervain's thyroiditis) Inflammation of the thyroid gland (usually to viral etiology) It leads to a release of stored thyroxin and thyrofoxicosis features, followed by hypothyroidism features due to the destruction of the thyroid cells. Viral infection is the most common cause Clinical features: Painful neck Features of hyperthyroidism initially Later — features of hypothyroidism Diagnosis: High T3, T4 (initially) then later will be decreased High ESR Decreased RAIU in all parts of the thyroid Treatment: Steroid, NSAl Ds (aspirin) Treatment of hyperthyroidism initially Later, the patient will remain hypothyroidism and will need thyroxin Sick euthyroid syndrome (Nonthyroidal illness) Any acute, severe illness can affect the circulating TSH and thyroid hormones in the absence of any thyroid disease Unless a thyroid disorder is strongly suspected, routine thyroid function testing should be avoided in acutely ill patients. Lab investigations: Low T3 syndrome: Low free T3 with normal T4 and TSH (the most common pattern) Low T4 syndrome: reduced T3 and T4 due to accelerated consumption. TSH may be reduced, normal or increased Treatment. No treatment is needed; the changes are reversible upon recovery from the systemic illness Page 161 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Parathyroid gland There are 4 parathyroid glands that are anatomically adjacent to the thyroid gland. Parathyroid hormone (PTH) regulates the serum calciumlevel Calcium regulation PTH affects the serum calcium by the following mechanisrrb: o Increase urinary reabsorption of calcium o Increase intestinal calcium absorption o Extracts calcium from bones into the blood Vitamin D effects on the serum calcium o Increase urinary reabsorption of calcium o Increase intestinal calcium absorption o Increase calcium deposition to the bone Calcium effects on PTH: o High serum calcium will suppress PTH release o Low serum calcium will stimulate PTH release Hypercalcemia The most common cause of hypercalcemia is primary hyperparathyroidism If hypercalcemia is severe and symptomatic, there is a high prevalence of malignancy due to PTH-like particles Causes of hypercalcemia: Primary hyperparathyroidism (most common cause) Vitamin D intoxication Sarcoidosis Thiazide diuretics Hyperthyroidism Malignancy: Multiple Myeloma, or Metastasis to bone Clinical features: Usually asymptomatic Psychiatric symptoms (confusion, depression, psychosis) Gl: Constipation, abdominal pain Cardiovascular: short QT syndrome and hypertension Renal: nephrolithiasis, DI, renal insufficiency, polyuria Page 162 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Treatment: I. V normal saline (first line) Furosemide (Lasix) — use with caution. Calcitonin has a faster effect than Bisphosphonates Bisphosphonates (inhibit bone resorption) Surgical removal of the adenoma Mithramycin (used to treatment of hypercalcemia inmalignancy) Steroids (treat hypercalcemia in sarcoidosis) Hypocalcemia (tetany) Tetany: increased excitability of peripheral nerves due tohypocalcemia or alkalosis Causes: Primary hypoparathyroidism: post-thyroidectomy (mostcommon cause) Hypomagnesemia (magnesium is necessary for PTH releasefrom the gland; hypomagnesemia leads to increase urinaryloss of calcium) Renal failure (kidneys are unable to activate Vitamin D into1,25 (OH) vitamin D) Vitamin D deficiency Genetic disorders and fat malabsorption Alkalosis (metabolic or respiratory) Low albumin status (Pseudohypocalcemia) Pseudohypocalcemia: Normal serum Calcium is 8. 4 10. 6 mg/d L Normal serum Albumin is 3. 5 5. 5 g/d L (mean = 4. 0) Every I g/L drop in albumin will result in 0. 8 mg/d L drop in serum calcium. Example on corrected calcium calculation: Consider serum albumin is 2. 5 g/L, and serum calcium is 7. 8 mg/d L. Corrected calcium = 0. 8 * (4. 0 — serum albumin) + serum ca. Corrected calcium = 0. 8 * (4 — 2. 5) + 7. 8 = 9 mg/d L. So, this is a case of Pseudohypocalcemia, not true hypocalcemia. Table 27: Pseudohypocalcemia and corrected calcium Page 163 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Clinical features: In children: (carpopedal spasm, stridor, convulsions) In adults: tingling in hands, feet, and around the mouth, muscle cramps, Psychosis, abdominal cramps Special signs: Trousseaus sign (carpal spasm after inflation of cuff on the arm) Chvostek's sign (twitching of facial muscles after facial nerve tapping) Peroneal sign (taping on Peroneal nerve results in dorsiflexion and abduction of the foot) o Erb's sign (motor nerve can be stimulated by low current < 5 milliamperes) Prolonged QT interval in ECG Treatment: Oral or I. V calcium Vitamin D replacement For hypomagnesemia, administrate Mg S04 Correction of alkalosis Hyperparathyroidism It can be primary, secondary Primary: adenoma, hyperplasia, or carcinoma of theparathyroid gland Secondary: high PTH in response to low serum calcium (CRF, malabsorption, rickets... ) Clinical features: Primary hyperparathyroidism: o Features of hypercalcemia o Bone pain and pathological fractures Secondary hyperparathyroidism: o Features of hypocalcemia Diagnosis: Primary hyperparathyroidism: High serum calcium and high PTH High Alkaline Phosphatase o High chloride o Low serum phosphate Imaging to localize the pathology Page 164 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Secondary hyperparathyroidism: o Low serum calcium o High PTH level o Features of the cause Treatment: Primary type: o Treat hypercalcemia o Remove the cause (e. g., adenoma removal) Secondary type: o Treat hypocalcemia o Correct the cause Hypoparathyroidism Causes: Postoperative hypoparathyroidism, after thyroid surgery, is the most common cause Idiopathic Pseudohypoparathyroidism (tissue resistance to PTH) Pseudohypoparafhyroidism: is a congenital resistance to parathyroid hormone leading to hypocalcemia, hyperphosphatemia, high PTH and low IQ, short stature, and short fourth and fifth metacarpals. Pseudopseudohypoparathyroidism: will present with the same morphological features of pseudohypoparathyroidsm but with normal serum calcium, phosphate, and PTH Clinical features of primary hypoparathyroidism: Tetany (in severe cases) Features of hypocalcemia Page 165 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Familial hypocalciuric hypercalcemia (FHH) It is an autosomal dominant disorder caused by a calcium sensor defect that increases the set point for the serum calcium It can be diagnosed early in childhood by serum and urinary calcium concentrations Pathogenesis: Abnormal sensing of the blood calcium by the parathyroid gland and renal tubule, causing inappropriate secretion of PTH and excessive reabsorption of calcium in the distal renal tubules This will lead to hypercalcemia and hypocalciuria Diagnosis: Most cases are detected during family screening Elevated serum calcium and PTH. Low urine calcium Low urinary calcium:creatinine ratio Treatment: Usually asymptomatic and needs no treatment Total parathyroidectomy can be beneficial The condition is not responsive to diuretics or bisphosphonates Diagnosis Primary hyperparathyroidism Secondary hyperparathyroidism Tertiary hyperparathyroidism Hypoparathyroidism FHH Vitamin D deficiency Pseudo-hypoparathyroidism Pseudo-pseudo-hypoparathyroidism Ca PTH P04 1 I 1 Normal Additional notes High urine Ca:creatinine ratio Reduced Ca enhances PTH History of CKD Low urine Ca:creatinine ratio Specific morphological features Specific morphological features Table 28: Differential diagnosis of parathyroid disorders Page 166 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Adrenal gland Anatomy: Two adrenal glands, located normally at the upper pole ofboth kidneys They are composed of cortex and medulla and covered bya capsule The cortex is composed of 3 layers: o Zona glomerulosa: it secrets aldosteroneo Zona fasciculata: it secrets cortisoneo Zona reticularis: it secrets androgen Medulla secrets epinephrine and Norepinephrine Hypercortisolism (Cushing's) Increase secretion of cortisone by adrenal glands Cushing's syndrome is used interchangeably withhypercortisolism Cushing's disease is a term used for pituitary overproductionof the ACTH hormone Causes: Pituitary tumor (ACTH-secreting tumor) Cushing's disease(most common 70%) Adrenal tumor (decreased ACTH) Ectopic ACTH production Iatrogenic: steroid administration Causes of Ectopic ACTH secreting tumors: Small cell lung cancer Bronchial carcinoid Pheochromocytoma Medullary thyroid cancer Clinical features: Hypertension, hyperglycemia, hypokalemia Fat redistribution: Moon face, weight gain / central obesity, buffalo hump, thin extremities Skin: Thinning of skin, abdominal striae, decreased wound healing, easy bruising, hirsutism, acne, skin pigmentation Muscle weakness (proximal muscle) Sexual disturbances, edema, amenorrhea Psychiatric symptoms (e. g., depression) Page 167 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diagnosis: Low dose (1 mg) dexamethasone suppression test ACTH levels High dose (8 mg)dexamethasone suppression test CT or MRI to localize the pathology Petrosal sinus sampling to confirm Cushing's disease when microadenoma does not show in imaging Other labs: hyperglycemia, hyperlipidemia, Hypokalemia, metabolic alkalosis Cushing's syndrome Confirmed by low dose dexamethasone challage High ACTH level Pe orm high ose dexamethasone challage test Low ACTH level Ectopic Steroid usage or Adrenal pathology ACTH supressed ? Pitutiary adenoma ACTH not supressed ? Ectopic ACTH Figure 8: Diagnostic approach to Cushing's syndrome Treatment: Pituitary adenoma: transsphenoidal excision Adrenal source: adrenalectomy of the affected side For Ectopic ACTH secretion: treat the cause For iatrogenic: stop steroid use if possible Petrosal sinus: is the venous drainage of the pituitary gland, if imaging fails to localize the pituitary adenoma, then microadenoma is suspected, and petrosal sinus sampling will confirm the diagnosis. Page 168 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Hypoadrenalism (Addison's disease) Chronic primary adrenal insufficiency Note that acute adrenal insufficiency is called adrenal crisis Causes: Autoimmune (most common cause 80%)-Infection (HIV, TB) Bilateral adrenalectomy Metastatic cancer in adrenal glands Clinical features: Weakness, weight loss, fatigue, vomiting, fever, constipation, abdominal pain, impotence, syncope, postural hypotension, loss of axillary hair Hyperpigmentation of skin (due to increased MSH), Not present in secondary adrenal insufficiency Hypotension Vitiligo (autoimmune process) Diagnosis: Hyperuricemia, hyperkalemia, hypercalcemia Hyponatremia, hypoglycemia, metabolic acidosis Abdominal CT scan Specific tests: o Serum cortisol (low) and ACTH (high) o Cosyntropin stimulation test (most specific test) o Anti-adrenal antibodies 50% o Low serum atdosterone Treatment: Hormone replacement Low High Sodium Urea Blood sugar Potassium Serum cortisol Calcium Serum aldosterone ACTH Table 29: Lab tests in primary hypoadrenatism Secondary hypoadrenalism: It is caused by hypothalamic or pituitary disease or long-term steroid suppression; aldosterone remains normal in this case because it is controlled by the renin-angiotensin system. page 169 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Adrenal crisis It is a medical emergency caused by sudden and marked insufficiency of adrenocortical hormones Precipitating factors: Stress (trauma, infection, hemorrhage, surgery, hypotension) Sudden withdrawal of chronic high-dose steroid therapy Clinical features: Dehydration, headache, confusion, coma Hypotension (shock) Hypoglycemia Nausea, vomiting, diarrhea, abdominal pain Hyponatremia and hyperkalemia High urea Treatment: Hydrocortisone injection (first step) I. V fluids Treatment of hypoglycemia Antibiotics Shock management Primary hyperaldosteronism Hypersecretion of aldosterone despite low renin and hypertension Causes: Adrenal adenoma (Conn's syndrome) Adrenal hyperplasia Adrenal malignancy (rare) Diagnosis: Suspected if HTN + Hypokalemia + metabolic alkaiosis Aldosterone:renin ratio > 20 (best initial test) 24 hours urinary aldosterone Locar:ze tumor or hyperplasia by CT or MRI (best) Treatment: Surgery for tumor Spironolactone for hyperplasia Spironolactone (Aldactone) is an anti-androgenic drug, so it causes gynecomastia and decreased fibido Page 170 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Pheochromocytoma It is a tumor of the medulla of the adrenal gland thatsecretes epinephrine and norepinephrine, It can be associated with other conditions like (MEN 11B,neurofibromatosis, and Von Hippel Lindau syndrome) malignant, 10% bilateral, 10% familial, and 10% extra-adrenal Clinical features: HTN (paroxysmal or persistent) Sweating Tachycardia Weight loss Tremor Hyperglycemia, hypercalcemia, and erythrocytosis Diagnosis: Free metanephrine level in plasma (initial test) 24 hours urinary vanillylmandelic acid 24 hours urinary catecholamines 24 hours urinary metanephrine (the most accurate test) Imaging to localize the tumor Treatment: Phenoxybenzamine (alpha-blocker) Non-cardioselective beta-blockers (e. g., propranolol) Surgical removal (the definite treatment) Non-cardioselective beta-blockers should be used if significant tachycardia occurs after the alpha blockade. Beta-blockers should not be administered until an adequate alpha blockade is achieved because unopposed alpha-adrenergic receptor stimulation can precipitate a hypertensive crisis. However, cardioselective beta-blockers may be used. Page 171 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diabetes mellitus (DM) DM is a clinical syndrome characterized by hyperglycemia due to an absolute or relative insulin deficiency. There are two common types of DM (Type 1 and type 2) Metabolism of glucose: The blood-brain barrier is not permeable to free fatty acids, so it depends on glucose as a main source of energy Glucose enters circulation by the gut (from food) or by the liver (gluconeogenesis and glycogenolysis) Insulin and glucagon are regulatory hormones of glucose; they are synthesized and secreted by the pancreas Insulin is also responsible for fatty acid metaboiism and causes triglyceride accumulation in the body, while low insulin levels can activate lipolysis. Type 1 DM An autoimmune disease destroys insulin-secreting cells in the pancreas; it will remain asymptomatic until 90% of beta cells are destroyed and usually starts before 3C)-35 years old Glutamic acid antibodies (GAD antibodies) have a role in pathogenesis, but it is not useful for diagnosis or screening TIDM is also Association with HLA-DR3 or HLA-DR4 Like any other autoimmune disease, it can be associated with other autoimmune diseases like Addisonts disease, pernicious anemia, and Vitiligo There is 35% concordance between monozygotic twins in Tl DM but 100% concordance between monozygotic twins in T2DM Environmental factors play a role in Tl DM, like smoked food, viral infections, or cows milk administration in infant life (bovine serum albumin is implicated in the development of Page172 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Metabolic and clinical features: Features of TIDM do not manifest until 90% of befa cells are destroyed. Insulin deficiency starts to manifest, and hyperglycemia results in a toxic effect on the remaining beta cells and thus more profound, rapidly progressive insulin deficiency that leads to: Lipolysis: weight loss, ketogenesis, and metabolic acidosis Hyperglycemia: osmotic polyuria and dehydration Dehydration can lead to renal impairment, hyperosmolarity, polydipsia, and hyperkalemia (shifting of out of cells) The summary of the TIDM presentation: Weight loss Metabolic acidosis with ketogenesis (DKA) Polyuria, Polydipsia, and polyphagia Dehydration and acute renal failure Treatment: Insulin (OHA are not beneficial) The target AIC target is < 7% Treatment of complications if present (e. g., DKA) Type 2 DM The patient has decreased insulin level, but to a lesser extent than Tl DM, and is usually associated with insulin resistance. Environmental and genetic factors are implicated in the development of T2DM Obesity and a sedentary lifestyle (under-activity) are important risk factors T2DM usually affects older ages Metabolic and clinical features: In T2DM, insulin suppresses lipolysis, and thus weight gain is a prominent feature, while ketosis and metabolic acidosis will be rare Slowly growing hyperglycemia leads to less severe or even absent symptoms of hyperglycemia The patient may present with mild generalized fatigue, Polyuria, polyphagia, and Polydipsia for a long period Page 173 | INTERNAL1-17AFEEF-MERGED-1.pdf |
The summary of the T2DM presentation: Mild fatigue for a long period Polyuria, Polyphagia, and Polydipsia If a stressful event occurs, increased counterregulatory hormones will lead to hyperglycemic hyperosmolar nonketotic coma (HHS) DKA is very rare in T2DM Treatment: Lifestyle modifications (initially for 3 months) Oral hypoglycemic agents: o Start if there is no glucose improvement with the lifestyle modifications for 3 months o Provide a single agent if the AIC level is less than 9% o Provide two agents if the AIC level is more than 9% o A combination of more than OHA is possible with paying attention to their side effects and interactions. Insulin: Used for patients who are not responding or cannot tolerate OHA Hb Alc target in DM treatment: If a young educated patient and easily controlled (on lifestyle modifications only or lifestyle modifications + Metformin), an AIC target of less than 6. 5% is acceptable If the patient is on any drug that can cause hypoglycemia (e. g., sulfonylurea), the AIC target of less than 7% is appropriate. Definition Onset Obesity Treatment Complication Insulin deficiency Childhood Not related Insulin dependent DKAT2DM fnsulin resistance Adulthood Related Non-insulin dependent HHS Table 30: Comparison between TIDM vs. T2DM Page 174 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Prediabetes (Pre-DM) It is not a disease but rather a risk category These patients are at risk of developing DM later in their lives Diagnosis of Prediabetes: Impaired fasting glucose (IFG): FBS 100-125 mg/dl Impaired glucose tolerance (IGT): 2h 75 g OGTTI 40-199 mg/dl Management: Lifestyle modifications (diet, exercise, stop smoking, control HTN, control dyslipidemia) Metformin especially for: o Those who are > 60-year-old o Those with high BMI > 35 kg/m2 o Women with a history of gestational DM Maturity onset diabetes of the youth (MODY) Genetic defect (autosomal dominant) of beta-cell function leads to decreased insulin secretion. The incidence is between 9 and 25 years old. Criteria for diagnosis: Diabetes is diagnosed in 3 generations in the family. At least one family member diagnosed under the age of 25 years Treatment of DM in pediatrics: Insulin is the drug of choice for DM in pediatrics Lab tests and diagnostic criteria Urinary glucose level is not a reliable indicator for DM. It may increase due to a decreased urinary threshold (e. g., pregnancy and young people) Random blood sugar (RBS) is a test done at a random time (non-fasting patients) Fasting blood sugar (FBS): testing after 8 hours of fasting. 2h 75 g OGTT is done 2 hours after adrinistering 75 grams of sugar to a fasting patient. Glycated hemoglobin (Hb Alc): reflects glycemic control over 3 months and is a measure of a patient's long-term diabetes control Page 175 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Lab test Normal range Pre-DM FBS (mg/d L) < 100 100-125 2 126 2h-P OGTT (mg/d L) < 140 199 2200 Hb A lc < 5. 6% 5. 7-6. 4% 2 6. 5% Table 3 1 : Glucose investigations and their ranges Diagnostic criteria of DM: any one of the following is diagnostic: The presence of DKA is diagnostic for TIDM Symptoms of DM + RBS 200 mg/dl or, One of the following On at least two separate occasions: o 126 mg/dl 0 2h 75 g OGTT2200 mg/dl o RBS 200 mg/dl DM complications Patients with T' DM should be assessed for DM complications 5 years after initial diagnosis with DM Patients with T2DM should be evaluated at the time of diagnosis because T2DM remains for many years undiagnosed and can cause complications at the time of diagnosis. Microvascular complications: Retinopathy — visual problems (After 5 years of DM) Nephropathy — renal impairment (After 10 years of DM) Neuropathy — sensory and autonomic can be affected (15 years of DM) Diabetic foot — ulceration, infection, and gangrene Macrovascular complications: CAD — Coronary Arterial Disease (the most common cause of death) PAD-Peripheral Arterial Disease CVA — Cerebrovascular Accidents Others: Cataract Infections (UTI, Pneumonia, soft tissue infections, TB) Page 176 | INTERNAL1-17AFEEF-MERGED-1.pdf |
To prevent diabetic complications. diabetic control should be achieved with near-normal glycemic control; this will reduce deaths and vascular complications related to DM. In the case of nephropathy, consider a cause other than DM if there is no retinopathy Health maintenance in DM patients: Pneumococcal vaccination for all patients Yearly eye examination Aspirin to all patients with DM who are > 30 years old Statin in patients with high LDL > 100 mg/dl ACEI/ARB for patients with DM + HTN and/or microalbuminuria. Foot examination for neuropathy and ulcers Table 32: Health maintenance for all DM patients Diabetic retinopathy Screening for retinopathy is recommended to be done yearty. This usually occurs in the first decade of DM development Stages: Non-profiferative stage: o Retinal vascular microaneurysms o Blot hemorrhages o Cottonwool spots Proliferative stage: o Neovascularization in response to hypoxiao Vitreous hemorrhage due to rupture of the new bloodvessels Macular edema: o It may occur at any stageo The most common cause of vision loss in DM patients(25% risk of moderate vision loss in the next 3 years) Page 177 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Treatment: Prevention is the most effective therapy: o Intense diabetic control o Intense blood pressure control o Temporary paradoxical worsening of retinopathy may occur within 6 — 12 months of improved glycemic control Proliferative retinopathy: pan-retinal laser photocoagulation Macular edema: focal laser photocoagulation Diabetic nephropathy It is the most common cause of renal failure in adults. This condition takes up to 10 years of diabetes to develop. However, high AIC is an independent risk factor for microalbuminuria. Albuminuria in individuals with DM is associated with an increased risk of cardiovascular disease. Individuals with diabetic nephropathy commonly have diabetic retinopathy as well Smoking will accelerate the development and progression of diabetic nephropathy Clinical and laboratory features: Persistent albuminuria (microalbuminuria) HTN, nephrotic syndrome, and renal failure Stages of diabetic nephropathy: (according to timing) In the first year after DM onset: o Renal hypertrophy and glomerular hyper-filtration o Results from afferent arteriolar dilatation and efferent arteriolar vasoconstriction o Increased GFR up to 140% During the first 5 years: o Mesangial volume expansion (resulted in Kimmelstiel-Wilson nodules) o Glomerular basement membrane thickening (more permeability to proteins) o Disruption of the podocytes (more protein loss) o CFR is returning to normal Page 178 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Persistent albuminuria 30-299 mg/day (Microalbuminuria):o Occurs after 5— 10 years after DM onseto May progress to macroalbuminuria (2 300 mg/day)o It cannot be detected by urinalysis Persistent albuminuria 2 300 mg/day (Macroalbuminuria)o Develops over the next 10 yearso Once macroalbuminuria develops, ESRD will occur in7 — 10 years o Blood pressure and pathologic renal changes arelikely to be irreversible at this time Screening: by albumin creatinine ratio (ACR): It should be done annually for all patients It should be done by an early morning specimen ACR > 2. 5 is considered microalbuminuria Management: Diabetic control is the most important step in themanagement Strict blood pressure control (< 140/90)ACE inhibitors or ARBs are the treatments of choice toreduce the progression of the disease and to reduce thelevel of microalbuminuria Strict control of dyslipidemia Page 179 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Diabetic neuropathy. Symmetrical sensory polyneuropathy: also called Gloves and stocking impairment, with loss of tendon reflexes in legs Asymmetrical motor neuropathy: thought to be due to an acute infarction in the lumbosacral plexus. present withweakness of proximal muscles associated with loss of tendon Mononeuropathy: motor or sensory, rapid dysfunction ofsingle peripheral or cranial nerve, most common nervesaffected are 3rd, 6th cranial nerves, sciatic andfemoral nerve. if more than one nerve is affected, it is calledmononeuritis multiplex Autonomic neuropathy: postural hypotension, loss ofbladder control, bradycardia, erectile dysfunction, constipation, diarrhea, incontinence, gastric atony. Diabetic ketoacidosis (DKA) DKA usually occurs in Tl DM, characterized by insulin deficiency with increasing counterregulatory hormones (GH, Cortisone, Adrenalin, Glucagon) It can present in T2DM, but that is very rare. Precipitants: Stress, infection, trauma Non-adherence to insulin therapy Expired insulin or bad insulin storage Pathogenesis: Lake of insulin-4 hyperglycemia —+ osmotic diuresis dehydration electrolyte disturbance (hyponatremia) Lake of insulin —+ lipotysis —+ ketone bodies metabolic acidosis deep rapid breathing (for compensation) Total body potassium is deficient, but normal serum potassium due to shifting to extracellular fluids Clinical features: Polyuria, polyphagia, and Polydipsia Dehydration Kussmaul's breath (deep rapid respiration) with fruity-smelling breath Altered mental status Non-specific abdominal pain Page180 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Lab investigations: ABCs: o Metabolic acidosis with a wide anion gapo Low bicarbonate level (the most accurate measureof severity of DKA) High ketones in urine and plasma Hyperkalemia, hypokalemia, or normal serum potassiummay present, but total body potassium is always low Hyperglycemia (Must be 250 mg/dl) Pseudo-hyponatremia Treatment: Keep NPO, insert Foley's catheter to monitor urine output Fluid (first line): o I liter over h, l, 2, 2. 4, 4, 6, then I-liter q8 hours o The fluid type is normal saline and should be shifted to D5W whenever the serum glucose level is < 250 mg/dl. o A slower infusion may be indicated in 18-25 year-old patients as they are at greater risk of cerebral edema Insulin: 0 0. 1 unit/kg/hour insulin infusion pump o Check serum glucose every I hour. Potassium (KCL): o Serum > 5. 3 m Eq/L: stop KCL infusion o Serum 3. 5-5. 3 m Eq/L: give 40 m Eq/L o Serum < 3. 5 m Eq/L: give > 40 m Eq/L under senior supervision. o Check serum potassium every 2—4 hours Sodium bicarbonates indications: o It is not used routinely as it rapidly reverses acidosis, impairs cardiac function, reduces tissue oxygenation, and promotes hypokalemia. o Sodium bicarbonate use is associated with the risk of brain edema. o It is indicated if severe acidosis is present (i. e., arterial p H < 7. 0) o Dose: 50 mmol/L in 200m L of sterile water with 10 m Eq/L KCI per hour for 2 hours until the p H is > 7. 0 Mannitol can be used if cerebral edema present Antibiotics for treatment of underlying infection Serum glucose, electrolytes, KFT, and ABGs, should be checked regularly to monitor improvement Page 181 | INTERNAL1-17AFEEF-MERGED-1.pdf |
H erosmolar H er I cemic s ndrome HHSAlso called hyperosmolar hyperglycemic nonketotic coma Usually, it OCCUß in T2DM Relative or partial insulin deficiency leads to decreasedglucose utilization and increased gluconeogenesis Lipolysis can be suppressed by a small amount of insurtn, sothere will be no ketone bodies formation Features: Hyperglycemia (Must be > 600 mg/dl) Polyuria, polyphagia, Polydipsia Dehydration along with electrolytes disturbances Hyperosmolarity Decreased level of consciousness Osmolarity = 2(Na+) + serum glucose + serum urea (all in mmol/l) Treatment: Intravenous fluid management: 0 1—3 L of 0. 9% normal saline over the first 2-3 hours o Use 0. 45% saline if there is hypernatremia (> 15 meq/L) o After hemodynamic stability is achieved, reverse the free water deficit (0. 45% saline then D5W); the calculated deficit should be reversed over the next 2 days. o As in DKA, Glucose Should be added to the intravenous fluid if the RBS is less than 250 mg/d L. Potassium repletion as in DKA Insulin therapy: o IV insulin bolus of 0. 1 unit/kg; then o IV insulin infusion constant rate of 0. 1 unif/kg/hour. o Double the insulin dose if serum glucose is not falfing o Reduce insulin infusion to 0. 5 u/kg/hour if serum glucose is less than 250 mg/d L. o Continue insulin infusion until the patient has resumed eating and can be transferred to subcutaneous insufin. page 182 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Parameter Age Disease type Glucose Acidosis Anion gap Osmolality Dehydration Insulin required DKA Young patients TIDM > T2DM 250 mg/dl Present (HC03-< 18) Increased > 290 m Osm/kg Less than HHS More HHS Elderly patients T2DM More than 600 mg/dl Not present (HCOs> 18) Normal > 320 m Osm/kg More prominent Less Table 33: DKA vs. HHS Hypoglycemia General considerations about hypoglycemia Hypoglycemia may be postprandial or fasting Postprandial hypoglycemia OCCUß within 5 hours after the last meal and is a common complication of gastrectomy or gastric bypass Whipple's triad: (diagnostic for hypoglycemia) Decreased level of consciousness Serum glucose < 55 mg/dl Improvement after administration of glucose Causes: Surreptitious (Insulin or OHA use) Insulinoma Chronic disorders (Severe CLD, CKD) Hypocortisolism Infant of diabetic mother Anorexia nervosa Treatment: Oral carbohydrates (for conscious patients) Intravenous dextrose (for unconscious patients) Intravenous glucagon can be used Correct the underlying cause For postprandial type, choose small meals containing fat, high-fibers, and complex carbohydrates Page 183 | INTERNAL1-17AFEEF-MERGED-1.pdf |
The appropriate dose of intravenous dextrose to treat hypoglycemia is 0. 25 g/kg. this is equivalent for 2. 5 ml/kg Use a central line to administrate dextrose ofconcentration of more than 10% to avoid the risk of thrombophlebitis. Table 34: Treatment of hypoglycemia in babies Surreptitious hypoglycemia It is the deliberate use of insulin or oral hypoglycemic agents (OHA) or insulin to induce hypoglycemia Diagnosis: History of access to OHA or insulin C-peptide level (during the event): o It is an indicator of high endogenous insulino It will be high in OHA usage o It will be low in insulin usage A urinary toxicology screen for OHA Treatment: Correct the hypoglycemia Adjust the dose of insulin or OHA if the patient is taking ahigh dose by mistake Appropriate reporting as indicated in your country Insulinoma Insulin is a peptide hormone composed of 51 amino acids Insulinoma is a benign tumor (usually < 2cm diameter) (few cases are malignant) An insulin-secreting tumor affects beta cells of the pancreas commonly found in the body and tail. It may present as a part of MEN type I Diagnosis: The patient has recurrent unexplained hypoglycemia. Hypoglycemia (Whipple's triad) C-peptide will be low during the attack Insulin levels will be high Imaging to locate the tumor Treatment: Treatment of hypoglycemia Surgical removal of the tumor page 184 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Other endocrine disorders Multiple Endocrine Neoplasia (MEN) Inherited (Autosomal dominant) rare syndrome in which multiple endocrine glands got Neoplasia The most common presentation in MEN I is hypercalcerria MEN MEN I MEN MEN lib Associated tumors Pancreatic, Pituitary, Parathyroid tumor Parathyroid, Pheochromocytoma, Medullary thyroid ca. Pheochromocytoma, Medullary thyroid cancer, Neuroma, and Marfanoid features Table 35: Types of Multiple Endocrine Neoplasia (MEN) MEN I MEN lla MEN lib Pan Pheo Neuro Para Pit Med Ma Figure 9: Mnemonics for MEN types Page 185 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Gynecomastia It is also called gynecomazia. It is defined as glandular breast tissue in males due to an imbalance between estrogen and androgen. Causes: Idiopathic (25%) Physiologic (persistence pubertal gynecomastia) (25%)Drug-induced ( I Cimetidine, Digoxin, Spironolactone Anti-androgen therapy, and some steroids. Hypogonadism (10%) o Klinefelter's syndrome o Autoimmune gonadal failure o Orchitis o Chemotherapy o Hypopituitarism o Kallmann's syndrome (Gn RH deficiency) o Hyperprolactinemia Androgen resistance syndromes Estrogen excess: o Liver failure o Estrogen-secreting tumors (testes, adrenal) o HCG secreting tumor (testes, lung) Diagnosis: Cfinical diagnosis A detailed history and Drug history are important Treatment: Remove the cause if possible Surgical removal for cosmetic reasons page 186 | INTERNAL1-17AFEEF-MERGED-1.pdf |
Obesity It is defined as the body mass index of 30 kg/m2 Obesity increases the rate of mortality and morbidity because of its association with insulin resistance, DM, HTN, dyslipidemia, stroke, IHD, peripheral arterial diseases, Osteoarthritis, GERD, OSA, and many other conditions. The body mass index = weight in kg/(height in meters)2 Body mass Index (BMI) estimation for adults: Underweight Normal weight Overweight Obesity< 18. 5 kg/m2 18. 5-24. 9 kg/m2 25-29. 9 kg/m2 2 30 kg/m2 Table 36 Normal and abnormal values of BMI for adults Management: The reasonable initial goal is the loss of 0. 5— I kg of weightper week Combined diet and exercise therapy (exercise is not effective as monotherapy) Pharmacologic therapy like gastric and pancreatic lipase inhibitors (Orlistat) may be used. Bariatric surgeries are indicated if the BMI of > 40 kg/m2 or > 30 kg/m2in the presence of obesity-related conditions like (OSA, DM, OA) o Improves the quality of life and reduces mortality o Improves glycemic control for DM patients o Reduce the use of medications Types of bariatric surgeries: Banding procedure: a band is placed around the upper part of your stomach to create a small pouch to hold food Gastric bypass: involves creating a small pouch from the stomach and connecting the newly created pouch directly to the small intestine Sleeve about 75% of the stomach Page 187 | INTERNAL1-17AFEEF-MERGED-1.pdf |
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