Kingdom of Bahrain Arabian Gulf University College of Medicine and Medical Sciences

1. Kingdom of BahrainArabian Gulf UniversityCollege of Medicine and Medical Sciences Internal Medicine Notes Nephrology Prepared by: Ali JassimAlhashli Based on: Kaplan Step 2 CK Internal Medicine

2. Acute Renal Failure (ARF) • Definition: it is the rapid rise in Blood Urea Nitrogen (BUN) or creatinine within a period of: • Hours: rhabdomyolysis or contras-induced renal failure (CT-scan). • Days-weeks: aminoglycoside toxicity or post-streptococcal glomerulonephritis. • Important definitions: • Renal insufficiency (azotemia): renal failure but no to the point in which you need dialysis. Azotemia means the accumulation of azolegorups or nitrogen in the blood. • Uremia (End-Stage Renal Disease): severe renal failure in which you need dialysis to save patient’s life. With uremia the patient has: severe acidosis, fluid overload, hyperkalemia, change in mental status, anemia and hypocalcemia. • Classification of ARF: • Pre-renal azotemia: there is hypoperfusion to the kidneys. • Intra-renal azotemia: there is glomerular or tubular defect. • Post-renal azotemia: there is decreased drainage from the kidneys. • Diagnostic tests: • BUN: • It is elevated in all forms of renal failure. • Falsely-elevated: high dietary protein; GI bleeding. • Falsely-decreased: liver disease or malnutrition. • Creatinine: • It is the main measure of renal function. • Creatinine is a metabolic product of skeletal muscles. • Creatinine clearance is a good estimate of Glomerular Filtration Rate (GFR) but it has to be adjusted to weight. • Creatinine only rises at a level of 0.5-1 point/day.

3. Pre-Renal Azotemia • Definition: renal failure which occurs due to decreased perfusion to the kidney. • Etiology: • Hypovolemia: severe vomiting or diarrhea, hemorrhage, burns and Addison’s disease. • Hypotension: in shock! • Decreased cardiac output: patients with CHF might have fluid overload and edema but intravascular volume is depleted and kidneys are hypoperfused due to inadequate cardiac pumping. • Low albumin states: in malnutrition or nephrotic syndrome. • Renal artery stenosis. • Investigations: • BUN:creatinine ratio = 20:1 • Low urine sodium (>20). • Low fractional excretion of sodium (>1%). • High urine osmolality (<500). • Renal artery stenosis: • Although patient might have systemic hypertension but this doesn’t matter because perfusion to kidneys will be decreased due to obstruction of renal arteries. This will result in increased BUN and creatinine. • This condition might get worse with the use of ACE-inhibitors which markedly diminish blood flow to kidneys. ACE inhibitors work by causing vasodilation of efferent arterioles. • Diagnosis: Doppler ultrasound and definitive diagnosis with Ct-scan. • Hepatorenal syndrome: • There is renal failure based on the presence of liver failure (KIDNEYS ARE NORMAL!). • BUN and creatinine will increase due to intense vasoconstriction of afferent arterioles resulting in decreased renal perfusion. • Diagnosis: • Exclude any diseases of the kidney. • Your diagnosis is confirmed by no improvement in renal function after administrating 1.5 L of colloid (e.g. albumin) to the patient. • Treatment: octreotide might be useful but the best treatment is liver transplantation.

4. Post-Renal Azotemia • Definition: renal failure which occurs due to BILATERAL obstruction of urine flow from kidneys. • Etiology: a stone/clot in urinary bladder, bladder cancer, neurogenic bladder, prostate hypertrophy/cancer or bilateral ureteral disease. • Clinical presentation: patient presenting with oliguria/anuria. • Diagnosis: • Physical examination: distended bladder. • Renal ultrasound/CT: bilateral hydronephrosis. • Post-voiding residual volume: < 50ml • BUN:creatinine ratio = 20:1 (but with prolonged obstruction it will reach 10:1), low urine sodium (>20), low fractional excretion of sodium (>1%). • Treatment: • Relieve the cause of obstruction. • Notice that complete recovery of renal function is possible when obstruction is treated within 10-14 days.

5. Intra-Renal Azotemia • Acute Tubular Necrosis (ATN): • Definition: renal failure due to tubular damage. • Etiology: • Severe hypoperfusion of kidneys resulting in ischemia of tubular cells that is followed by necrosis and sloughing-off of these dead cell into the urine (patient will say that he is passing tissues in the urine!) → they appear as muddy, brown casts. • Toxic injury to kidneys caused by drugs such as aminoglycosides or amphotericin. Usually, patients with ATN have combination of hypoperfusion and toxic injury. • Clinical presentation: there are 3 phases of ATN (not seen in all patients): • Prodrome: it is the time between acute renal injury and onset of renal failure. • Oliguric phase (>400 ml of urine/24 hours) or anuric phase (>100 ml of urine/24 hours). • Postoliguric phase: during which all urine not previously excreted will leave the body in a vigorous polyuria. • Diagnosis: BUN:creatinine ratio = 10:1, high urine sodium (<40), high fractional excretion of sodium (<1%) and low urine osmolality (>350). • Treatment: once ATN occurs there is no medical therapy to reverse it! Support the patient with hydration and wait for the outcome. If the condition is severe and life-threatening → dialysis.

6. Intra-Renal Azotemia • Allergic Interstitial Nephritis (AIN): • Etiology: • Medications (70% of cases):penicillins, cephalosporins (except ceftriaxone), sulfa drugs, allopurinol, rifampin and quinilones. There must be an exposure to these medications for several weeks before developing renal injury. • Infections: Legionella, Streptococci, CMV and Rickettsia. • Autoimmune disorders: SLE, sarcoidosis and Sjogren syndrome. • Idiopathic (8% of cases). • Clinical presentation: • Fever (80% of patients). • Rash (25-50% of patients). • Joint pain (because AIN acts as serum-sickness). • Hematuria. • Diagnosis: • Blood: eosinophilia and ↑IgE level. • Urinalysis: eosinophiluria (more common than eosinophilia and detected by Hansel stain or Wright stain), hematuria and proteinuria. • Biopsy (most accurate diagnostic test). • Treatment: patient resolves spontaneously after stopping the offending agent. The pleomorphic infiltrate, including binucleatedeosinophils (arrows)

7. Intra-Renal Azotemia • Rhabdomyolysis: • Etiology: sudden, sever crush injury; severe exertion; seizures or medications (such as statins). • Clinical presentation: • Painful muscles. • Dark urine (due to the presence of myoglobin which is considered as a pigment that it directly toxic to tubular cells of the kidney). • Diagnosis: • Most important test to be done for a patient presenting with rhabdomyolysis is: ECG and potassium level (why?) → because these patients will have hyperkalemia and might die due to fatal arrythmias (tall T-wave on ECG). • The, you will do urinalysis which will show: (+) dipstick; (-) RBCs. • To confirm your diagnosis: markedly elevated CPK. • Treatment: • If there is hyperkalemia: give calcium chloride or calcium gluconate. • Hydration + mannitol (as a diuretic) to decrease the period of exposure between the nephrotoxicmyoglobin and tubular cells of the kidney. • Alkalinize the urine with sodium bicarbonate.

8. Intra-Renal Azotemia • Crystals: • Oxalic acid: • The most common cause of acute hyperoxaluria which results in renal failure is ethyelen glycol overdose in a suicidal patient who ingests antifreeze. Notice that chronic hyperoxaluria and kidney stones can be caused by Crohn’s disease. • Diagnosis: • Metabolic acidosis with increased anion gap. • Urinalysis: oxalate crystals (envelope-shaped). • Treatment: • Fomepizole infusion: to prevent the formation of oxalic acid from ethylene glycol. • Dialysis: to remove ethylene glycol from the body. • Sodium bicarbonate: to correct metabolic acidosis. • Uric acid: • Etiology: acute renal injury with uric acid is caused by tumor-lysis syndrome. This explains why it is important to hydrate and give allopurinol with alkalinization of urine for patients with leukemia/lymphoma before starting chemotherapy. Notice that chronic uric acid with formation of stones is seen in patients with gout (hyperuricemia). • Diagnosis: uric acid crystals detected by urinalysis.

9. Intra-Renal Azotemia • Hypercalcemia: • Increased calcium concentration can result in depositions in renal tubules leading to formation of stones. • The most common cause of hypercalcemia is primary hyperparathyroidism. • If this hyperparathyroidism is associated with renal impairement → surgical removed of parathyroid glands. • Toxins: • Toxins which can cause renal failure or ATN are: aminoglycosides, amphotericin, NSAIDs, cyclosporine and heavy metals (lead, mercury and gold). • How to differentiate between direct effect of these toxin and AIN? → in AIN, symptoms will appear from the first dose and patient will have fever, skin rash, joint pain and eosinophilia/ eosinophiluria. • Aminoglycosides: • Tobramycin is the least nephrotoxic when compared to gentamicin and amikacin. • Toxicity takes 5-10 days to appear and it is reversible. • Hypokalemia and hypomagnesemia predispose to aminoglycoside toxicity. • Aminoglycosides are also ototoxic (to neural cell of inner ear). • Amphotericin: • After using it for several days to weeks it will result in: high creatinine, low potassium, low magnesium and low bicarbonate. • Toxicity is reversible when stopping medication. • Atheroembolic disease: • Look for a patient who undergoes catheterization and angioplasty who develops renal failure several day later. • This condition is associated with: eosinophilia, low complement and bluish discoloration of fingers and toes. • There is no therapy for atheroembolic disease. • Contrast agents: • Contrast materials used in CT-scan can result in renal failure within 12-24 hours of contrast use (especially in elderly, diabetics and hypertensive patients). • Rise in creatinine peaks at day 3-5. BUN:creatinine ratio = 20:1 (similar to pre-renal azotemia). • To prevent it, hydrate the patient with 1-2 liters of normal saline over 12 hours before the procedure.

10. Intra-Renal Azotemia • Analgesic nephropathy: • NSAIDs can cause renal failure by several mechanisms: • Direct toxic effect on renal tubules. • Papillary necrosis. • Interstitial nephritis. • Membranous glomerulonephritis. • Inhibition of vasodilatory prostaglandins in afferent arterioles. • NSAIDs result in renal failure in those patient who already have an underlying renal insuffieciency (e.g. elderly, diabetic or hypertensive patients). • Pyuria (presence of pus in the urine) + negative urine culture can be a clue for the diagnosis. • Papillary necrosis: • Occurs in patients with: • Sickle cell disease. • Diabetes. • Chronic pyelonephritis. • Urinary obstruction. • NSAIDs. • Clinical manifestations (similar to acute pyelonephritis): fever, flank pain, hematuria and pyuria BUT URINE CULTURE WILL BE NEGATIVE. • Diagnosis: CT-scan showing bumpy contours in renal pelvis.

11. Glomerulonephritis • Definition: it is an inflammation of the glomerulus caused by circulating antibodies, deposition of immune complexes or vasculitis. Notice that diabetes and hypertension result in glomerular disease and are considered as most common causes for NEPHROTIC syndrome and ESRD. • Clinical manifestations of glomerulonephritis: • Heumaturia with dysmorphic RBC casts. • Edema: caused by salt and water retention. Initially it is seen in peri-orbital area or scrotum but severe edema can occur anywhere in the body. • Hypertension: also caused by salt and water retention. • Proteinuria: > 2 grams/24 hours (notice that in nephrotic syndrome it reaches < 3.5 grams/24 hours). • Diagnosis: • The single most important test to diagnose glomerulonephritis is renal biopsy. • Wegner granulomatosis: • Definition: it is vasculitis of small-sized arteries commonly involving upper respiratory tract, lungs and kidneys. • Clinical manifestations: • Upper respiratory tract: sinusitis, chronic rhinitis and rarely nasal ulcers. • Lungs: cough, hemoptysis and dyspnea. • Kidneys: hematuria. • Diagnosis: • Presence of c-ANCA. • Definitive diagnosis is made with biopsy of any involved organ looking for: vasculitis and granulomas. • Treatment: cyclophosphamide and steroids.

12. Glomerulonephritis

13. Churg-strauss syndrome: • Definition: it is vasculitis of small and medium-sized arteries with chronic lung involvement, neuropathy, GI manifestations and renal involvement. • Clinical manifestations: patient usually has a history of asthma, eosinophilia or other atopic diseases. • Diagnosis: • Lab: ↑eosinphils and presence of p-ANCA. • Biopsy: granulomas + eosinophils. • Treatment: steroids and cyclophosphamide. • Goodpasture syndrome: • Definition: it is an idiopathic disorder involving lungs and kidneys due to presence of anti-basement membrane anitbodies. • Clinical manifestations: • Lungs: cough, hemoptysis and dyspnea. • Kidneys: hematuria and proteinuria. • Diagnosis: • Presence of anti-basement membrane antibodies. • Renal biopsy: linear deposits on immunofluorescence. • Treatment: steroids and plasmapheresis. • PolyarteritisNodosa (PAN): • Definition: it is a vasculitis of small and medium-sized arteries involving any site in the body with exception of lungs. • Clinical manifestations: • Neuropathy (70%). • Abdominal pain and GI bleeding. • Renal: hematuria and hypertension with renal failure. • Diagnosis: • Presence of p-ANCA. • It might be associated with active hepatitis B infection. • Abdominal angiogram (when GI manifestations are prominent). • Sural nerve biopsy (most accurate). • Treatment: steroids + cyclophosphamide. Glomerulonephritis

14. Glomerulonephritis

15. IgA nephropathy (Berger Disease): • It is the most common glomerulopathy worldwide and caused by deposition of IgA. • Clinical manifestations: • Look for a young Asian patient who has recent viral illness/pharyngitis and develops hematuria/hypertension 2-3 days later (this is to differentiate it from post-infectious glomerulonephritis which occurs 1-2 weeks following infection). • Diagnosis: • Serum IgA level is elevated in only 50% of patients. • Renal biopsy (definitive diagnosis): showing granular IgAdepositis. • Treatment: ACE inhibitors or steroids. • Prognosis: • 30% of patients will resolve spontaneously. • 40-50% of patients will progress to ESRD. • Post-streptococcal glomerulonephritis: • Etiology: it occurs 1-2 weeks following pharyngitis or skin infection with GABHS (S.pyogens). Notice that rheumatic fever occurs only with pharyngitis strains. • Clinical manifestations: • Cola-colored urine. • Hypertension. • Periorbital edema. • Diagnosis: • ASO test + AHT test. • Low C3 complement. • Renal biopsy: subepithelial humps on electron microscopy. • Treatment: most patients resolve spontaneously. Fluid overload and hypertension treated with diuretics. Glomerulonephritis

16. Cryoglobulinemia: • Clinical manifestations: • Purpuric skin rash. • Renal involvement. • Joint pain. • BUT THERE IS NO GI INVOLVEMENT AND THIS DIFFERENTIATES IT FROM HSP. • IT IS ASSOCIATED WITH CHRONIC HEPATITIS C AND LESS COMMONLY B. • Diagnosis: • ↑ESR. • ↓complement. • Positive RF. • Diagnosis is confirmed with the presence of cryoglobulins. • Treatment: • Treat the underlying chronic hepatitis with interferon and ribavirin. • If disease is severe: • Pulse doses of steroid. • Or plasmapheresis. • Diabetes: • One of the most common causes which leads to glomerular disease and ends with nephrotic syndrome and ESRD. • Patients with diabetes must be screened annually for: • Creatinine level. • Microalbuminuria(which is defined as abnormal protein excretion but > 300mg/24 hours. • Diabetic nephropathy is controlled mainly with ACE inhibitors. Glomerulonephritis

17. SLE: • Patients with SLE have different degrees of renal involvement. Some of them have asymptomatic hematuria/proteinuria while others end-up needing dialysis. Remember that lupus nephritis is the most common cause of disability in patients with SLE. • During flare-ups of the disease, lupus nephritis followed-up through the following: • ds-DNA: ↑ • Complement levels: ↓ • Diagnosis is made-up with renal biopsy. • Alport syndrome: • It is a genetic (X-linked) disease in which there is an inherited defect in type IV collagen resulting in a combination of: • Glomerular disease. • Sensoryneural deafness. • Congenital eye abnormalities. • Amyloidosis: • There are 2 types of amyloidosis: • AL: plasma cell dyscrasia causing deposition of protein derived from immunoglobulin light chains. This is associated with multiple myeloma. • AA: • Amyloid is produced as a proteinaceous material in association with different chronic infectious/inflammatory conditions (e.g. RA, IBD or multiple myeloma). • Clinical manifestations: • Renal: glomerulonephritis. • Heart: restrictive cardiomyopathy and arrhythmia (e.g. heart block). • Neuro: carpal tunnel syndrome. • GI: malabsorption. • There is macroglossia. • Diagnosis: biopsy of any involved organ + use of Congo red stain = green birefringence. • Treatment: malphalan and prednisone. Glomerulonephritis

18. Nephrotic Syndrome • It is characterized by: • Proteinuria (<3.5 grams/day): protein is excreted into urine when glomerular basement membrane loses its negative charge. • Hypoalbuminemia. • Edema: it is caused by salt and water retention + low oncotic pressure (due to loss of albumin). • Hyperlipidemia: it occurs due to loss of markers on the surface of lipoproteins (e.g. chylomicrons and LDL). Therefore, there is deficiency in clearing these lipids from the blood. • Hypercoagulable state: due to urinary loss of antithrombin III, protein C and protein S (natural anticogulants). • 1/3 of nephrotic syndrome is associated with systemic diseases such as hypertension and diabetes. • The most accurate test to determine the etiology of nephrotic syndrome is renal biopsy. • Treatment: • Steroid is effective in: membranous nephropathy, minimal change disease and membranoproliferativeglomerulonephritis. • If steroids do not work, try cyclophosphamide. • ACE inhibitors are used for all patients with proteinuria.

19. Nephrotic Syndrome

20. Nephrotic Syndrome • Focal-Segmental Glomeruolosclerosis (FSGS): • It is the most common form of nephrotic syndrome in adults. • Associated with: HIV and heroin use. • Not responding well to steroids (only 20-40%). • It may progress to ESRD within 5-10 years. • Minimal Change Disease: • It is the most common form of nephrotic syndrome in children. • Associated with: use of NSAIDs and Hodgkin’s lymphoma. • It responds well to steroids. • Electron microscopy shows: fusion of foot processes. • Membranous Nephropathy: • Associated with: cancers (lymphoma, breast cancer), infections (Chronic hepatitis B/C), NSAIDs, gold salts and lupus. • Responding to steroids. • Mesangial: • Mostly idiopathic. • Resistant to steoids. • Immunofluorescence shows: IgM deposits with expanded mesangium. • Membranoproliferative: • Associated with: chronic hepatitis and low serum complement.

21. Nephrotic Syndrome Focal-segmental glomerulosclerosis Minimal Change disease Membranous nephropathy

22. Urinalysis • Proteinuria: • Urine dipstick detects albumin but not other proteins. • Microalbuminuria: it is an abnormal excretion of albumin but > 300 mg/day. • Proteinuria can occur due to stressors: fever, CHF or excessive exercise. It can also occur due to prolonged standing (orthostatic proteinuria). • Hematuria: • Presence of RBCs in the urine due to bleeding from urinary bladder or the kidney. • Etiology: stones, cancer, glomerulonephritis, cystitis, prostatitis, bleeding disorders or trauma to urinary tract. • RBC casts from glumerular disease are dysmorphic. • Nitrites: • If gram-negative bacteria are present in the urine, they will reduce nitrate to nitrite (therefore it is considered as a marker of inflammation). • Bacteruria: • Presence of bacteria in the urine (positive urine culture). • Casts in the urine: • Hyaline casts: dehydration. • RBC casts: glomerulonephritis. • Broad,waxy casts: chronic renal failure. • Granular casts: ATN. • WBC casts: pyelonephritis or interstitial nephritis.

23. Urinalysis

24. End-Stage Renal Disease (ESRD) • Most common causes of ESRD are systemic diseases such as diabetes and hypertension. • What are the indications for dialysis? → life-threatening conditions which do not respond to medical therapy: • Fluid overload not responding to diuretics (e.g. furosamide). • Severe acidosis. • Hyperkalemia. • Encephalopathy. • Pericarditis. • Hemodialysis is used in 85% of patients while peritoneal dialysis is used in 15% of patients: • Complications of hemodialysis: hypotension, hemorrhage, septecemia, muscle cramps, nausea/vomiting and headache. • Common complications of peritoneal dialysis: exit site infection, peritonitis, pericatheter leakage, hydrothorax, hyperglycemia, hyperlipidemia and protein depletion. • Peritoneal dialysis is indicated for those: cardiovascular/hemodynamic instability, vascular access failure, unable to form a vascular access and patient wishes to be more free and moving. • Complications of ESRD: • Anemia: due to loss of eythropoietin production. This is treated by replacement of erythropoietin. Type of anemia: anemia of chronic disease (normochromic, normocytic). • Hypocalcemia/hyperphosphatemia: • Hypocalcemia: due to inability to produce the active form of vitamin D due to loss of 1α-hydoxylase function of the kidney. This is treated by vitamin D supplement. • Hyperphosphatemia: this is due to inability of kidney to excrete phosphate. This is treated with phosphate binders (e.g. calcium carbonate or calcium acetate).

25. End-Stage Renal Disease (ESRD)

26. Complications of ESRD (continued): • Renal osteodystrophy (osteitisfibrosacystica): because there is no production of active form of vitamin D there will be low calcium levels which in turn will stimulate parathyroid glands to produce more of parathyroid hormone that will result in bone resorption. • Hypermagnesemia: due to inability of the kidney to excrete magnesium. This is controlled by restriction of magnesium intake. • Hypertension and accelerated atherosclerosis: the most common cause of death in patients on dialysis is coronary artery disease! Your target blood pressure in these patients is >130/80 mmHg. • Infections: it is the 2nd most common cause of death in patients on dialysis. It occurs because neutrophils and other WBCs do not function well in a uremic environment. Most common organism: Staphylococcus (coming from the skin when puncturing it for dialysis procedure). • Bleeding: it occurs due to uremia-induced platelet dysfunction. This is managed be giving desmopressin to the patient which will increase the release of vWF and factor VIII resulting in adhesion and aggregation of platelets. • Dietary control: patients with ESRD must have a diet restricted in: salt (sodium), potassium, magnesium, phosphate and proteins. • Pruritis. • Renal tranplantation: • Survival is better in patients with renal transplant than in those on dialysis: • Renal transplant from a liver related donor: 70% 5-year survival. • Patient on dialysis: 30-40% 5-year survival. • After transplanting a kidney to a patient he will be set on: cyclosporine, tacrolimus and mycophenolate (all of them inhibitng the function of T-cells which mediate rejection of the organ). End-Stage Renal Disease (ESRD)

27. End-Stage Renal Disease (ESRD) • Classification of Chronic Kidney Disease (CKD): • Stage I: kidney damage with normal GFR ≥ 90 ml/min. • Stage II: GFR = 60-89 ml/min. • Stage III: GFR = 30-59 ml/min. • Stage IV: GFR = 15-29 ml/min. • Stage V: GFR > 15 ml/min (dialysis is definitely required).

28. Fluid and Electrolyte Disorders • Hyponatremia: • Definition: it is a low sodium level >135 mEq. 90% of sodium is extracellular. • Etiology: • Increased free water retention. • Urinary loss of sodium. • Seriumosmolality = (2 x sodium) + BUN/2.8 + glucose/18 • When BUN and glucose are normal → you can use the following equation = (2 x sodium) + 10 • Clinical presentation: • It varies from mild confusion and forgetfulness to seizures and coma. Notice that symptoms generally do not appear unless serum sodium level is > 125 mEq. • Symptoms depend mainly on how fast the level of sodium drops: • An acute drop in the level of sodium by 15-20 points will result in seizures and coma. • While the drop of the same amount but very gradually will be sustained by the patient with no symptoms! • Treatment: • Mild hyponatremia (e.g. patient has no symptoms): fluid restriction. • Moderate hyponatremia: normal saline (0.9% NaCl) + loop diuretic (e.g. furosemide). Saline will provide sodium while the diretic will cause free water loss. • Severe hyponatremia (e.g. seizures or coma): 3% hypertonic saline and V2-receptor antagonists. • Notice that sodium level must no be corrected rapidly otherwise this will result in central pontinemyelinolysis. Correct sodium level by 0.5 mEq/hour equal to a total of 12 mEq/24 hours.

29. Fluid and Electrolyte Disorders • Hyponatremia (continued): • Specific etiologies of hyponatremia: • Pseudohyponatremia: • Hyperglycemia: sodium level will drop 1.6 mEq/L for each 100 mg/dL increase in blood glucose above normal. When blood glucose level is increased this will cause shift of water outside the cell. • Hyperlipidemia: simply this a lab artifact. • Hypervolemiahyponatremia: this occurs in conditions in which there is increased free water retention due to secretion of ADH from posterior pituitary gland: • Congestive Heart Failure (CHF). • Nephrotic syndrome with low albumin level. • Liver cirrhosis. • Renal insufficiency. • Hypovolemichyponatremia: this occurs when there is loss of sodium with body fluid loss and the patient replaces it with free water: • GI losses: vomiting and diarrhea. • Skin losses: burns and sweating. • Diuretics. • Adrenal insufficiency (Addison’s disease). • ACE inhibitors. • Euvolemichyponatremia: • Psychogenic polydypsia: doesn’t occur unless patient drinks 15-20 L of water. • Diuretics. • ACE inhibitors. • Hypothyroidism. • Syndrome of Inaapropriate Secretion of ADH (SIADH).

30. Hyponatremia (continued): • SIADH: • Definition: increased secretion of ADH from posteror pituitary gland. • Etiology: • CNS disease: trauma, tumor, stroke or infection. • Pulmonary disease: pneumonia, TB, asthma or pulmonary embolism. • Neoplastic disease: lung cancer and cancers of pancreas, duodenum or thymus. • Medications: SSRIs, tricyclic antidepressants, haloperidole, vincristine and carabmazepine. • Diagnosis: • Decreased urine output. • Increased urine osmolality. • Increased urine sodium. • Increased ADH level. • Treatment: • Mild cases: fluid restriction. • Severe cases: hypertonic saline. • Hypernatremia: • Definition: it is increased serum sodium level (<145 mEq). • Etiology: • Loss of body fluids with no replacement with free water: sweating, burns and diarrhea. • Transcellular shift: rhabdomyolysis and seizure stimulate increased uptake of water by muscles resulting in hypernatremia. • Renal causes: central diabetes insipidus, nephrogenic diabetes insipidus, osmotic diuresis (DKA, non-ketotichyperosmolar coma, mannitol, diuretics). • Clinical manifestations: mainly neurologic ranging from lethargy and weakness to seizures and coma. • Diagnosis: mainly aiming to differentiate between central and nephriogenic DI by water deprivation test. • Treatment: normal saline but keep attention NOT to correct sodium by < 12mEq/24 hours otherwise causing cerebral edema. • Central DI: vasopressin. • Nephrogenic DI: diuretics. Fluid and Electrolyte Disorders

31. Fluid and Electrolyte Disorders

32. Fluid and Electrolyte Disorders

33. Hypokalemia: • Definition: it is low serum potassium level (>3.5 mEq). 95% of potassium is intracellular. • Etiology: • GI losses: vomiting and diarrhea. • Transcellular shift: alkalosis, increased level of insulin. • Urinary loss: diuretics, Conn syndrome (↑aldosterone), low magnesium (because normally magnesium decreases urinary loss of potassium). • Clinical manifestations: • Muscle weakness and when the condition is severe there might be paralysis. • Most serious complication being fatal arrhythmias. • Diagnosis: • Most important diagnostic test to be done is ECG to look for the presence of arrhythmia. Hypokalemia is associated with flattening of T-wave and presence of U-wave (a wave that occurs after the T-wave and represents purkinje fiber repolarization). • Treatment: • Potassium replacement by IV infusion (maximum of 10-20 mEq/hour compared to 0.5 mEq/hour when replacing sodium in hyponatremia). • Notice that rapid replacement of potassium can result in fatal arrhythmias. • Hyperkalemia: • Definition: it is high serum potassium level (<5.5 mEq). • Etiology: • Transcellular shift: acidosis or insulin deficiency. • Increased intake (oral or IV) usually accompanied by impaired excretion. • Pseudohyperkalemia: hemolysis, mechanical trauma during venepuncture. • Rhabdomyolysis. • Decreased urinary excretion: ESRD, adrenal insufficiency and potassium-sparing diuretics (spironolactone and amiloride). • Clinical manifestations: most important being fatal arrythmias. • Diagnosis: ECG looking for peaked T-wave with short QT-interval. • Treatment: calcium gluconate/chloride, resonium, glucose+insulin infusion, sodium bicarbonate → if all of these fail to correct hyperkalemia → dialysis. Fluid and Electrolyte Disorders

34. Fluid and Electrolyte Disorders

35. Fluid and Electrolyte Disorders

36. Fluid and Electrolyte Disorders

37. Acid/Base Disturbances (ABG Interpretation) • First of all, you must know the normal values of ABG: • pH = 7.35 – 7.45… (7.4). • PCO2 = 35 – 45 mmHg… (40 mmHg). • HCO3 = 22 – 26 mEq/L… (24 mEq/L). • What are the steps which you must follow when interpreting an ABG result? • First, look to the pH and comment if the patient has acidosis or alkalosis? • Acidosis: pH > 7.35 • Alkalosis: pH < 7.45 • Then, comment whether this acid-base disturbance is respiratory or metabolic? • Respiratory acidosis (↑PCO2): look for any causes of hypoventilation which leads to accumulation of CO2 that is considered to be an acid: • COPD. • Obesity. • Sleep apnea. • Depression of respiratory drive by opiates. • Effusions. • Suffocation. • Respiratory alkalosis (↓PCO2): look for any causes of hyperventilation which leads to washout of CO2 from the lungs: • Pain. • Anxiety. • Severe anemia. • Pulmonary embolism.

38. What are the steps which you must follow when interpreting an ABG result? • First, look to the pH and comment if the patient has acidosis or alkalosis? • Acidosis: pH > 7.35 • Alkalosis: pH < 7.45 • Then, comment whether this acid-base disturbance is respiratory or metabolic? (continued) • Metabolic acidosis (↓HCO3): causes are classified according to the anion gap (anion gap = (Na) – (HCO3 + Cl)… normal value = 8-12): • Low anion gap: • Multiple myeloma. • Low albumin level. • Lithium. • Normal anion gap: • Diarrhea. • Renal tubular Acidosis (RTA). • Ureterosigmoidostomy (it is a surgical procedure in which ureter are connected to sigmoid colon and considered as a part of treatment of bladder cancer in which urinary bladder has to be removed). • High anion gap (mnemonic: LA MUD PIE): • L: Lactate. • A: Aspirin. • M: Methanol. • U: Uremia. • D: DKA. • P: Propylene glycol. • I: Isoniazid and Isopropyl alcohol. • E: Ethyelen glycol. • Metabolic alkalosis (↑HCO3): can be caused by the following: • Loss of H: vomiting, Conn syndrome or diuretics. • HCO3 retention: bicarboate administration. • Movement of H into cells: hypokalemia. Acid/Base Disturbances (ABG Interpretation)

39. What are the steps which you must follow when interpreting an ABG result? • First, look to the pH and comment if the patient has acidosis or alkalosis? • Acidosis: pH > 7.35 • Alkalosis: pH < 7.45 • Then, comment whether this acid-base disturbance is respiratory or metabolic? • After that, look if there is compensation by body systems trying to bring the pH back to normal. • There are 2classifications: • Full compensation: in which pH completely returns back to normal range. • Partial compensation: in which pH doesn’t return back to normal range. Notice that with presence of compensation, both CO2 and HCO3 should move in the same direction (for example, if there is respiratory acidosis (↑CO2) → there will be retention of HCO3). If they do not move in the same direction → this indicated the presence of a mixed disorder. • Compensation of respiratory acidosis: • Acute respiratory acidosis: HCO3 increases 1 mEq/L for each 10 mmHg increase in PCO2. • Chronic respiratory acidosis: HCO3 increases 4 mEq/L for each 10 mmHg increase in PCO2. • Compensation of respiratory alkalosis: • Acute respiratory alkalosis: HCO3 decreases 2 mEq/L for each 10 mmHg decrease in PCO2. • Chronic respiratory alkalosis: HCO3 decreases 5 mEq/L for each 10 mmHg decrease in PCO2. • Compensation of metabolic acidosis: • Expected PCO2 = 1.5 x (HCO3) + 8 (± 2) • Compensation for metabolic alkalosis: • Expected PCO2 = 0.7 x (HCO3) + 20 (± 5) Acid/Base Disturbances (ABG Interpretation)

40. Acid/Base Disturbances (ABG Interpretation)

41. Adult Polycystic Kidney Disease • Definition: it is an autosomal dominant disorder which results in abnormal multiple cysts that develop and grow in kidneys. • Clinical manifestations: • Patient might be asymptomatic and found to have the disease with screening that is done for family members (as this disorder is inherited). • Or he might have flank pain, hematuria (gross/microhematuria), increased risk for UTIs and renal stones. • Extra-renal manifestations: • Hepatic cysts (40-60%). • Colonic diverticula. • Hypertension (50%). • Intracranial aneurysms (20%). • Mitral valve prolapse (25%). • Diagnosis: abdominal ultrasound or CT-scan. • Treatment: nonspecific aiming to treat complications (UTI, stones and hypertension).

42. Hypertension (HTN) • Essential HTN (95% of all HTN cases): • Definition: HTN is defined as a patient with blood pressure ≥ 140/90 mmHg on repeated examination (2-3 different readings). • In patients with diabetes and ESRD, it is preferred to keep blood pressure > 130/80 mmHg. • Patients with very severe HTN (≥ 160/100 mmHg) must be started initially with 2 Medications to control the blood pressure. • Stages of HTN: • Stage 1: systolic (140-159 mmHg); diastolic (90-99 mmHg). • Stage 2: systolic (≥160 mmHg); diastolic (≥ 100 mmHg). • Etiology: there is no specific cause of essential HTN but it is associated more with: • Advanced age. • Males (females will have equal prevalence after menopause). • Black population. • Clinical manifestations: • Most commonly, patient is asymptomatic! He is found to have high blood pressure with routine check-up or during investigation for another medical condition. • If patient presents with symptoms related to HTN, you have to think of 2 conditions: • Either it is a hypertensive emergency in which patient can present to emergency with stroke, subarachenoid hemorrhage, blurred vision, MI and hematuria. Diagnostic tests to be done are: head CT-scan, ECG, urinalysis with BUN and creatinine and fundoscopy. You have to lower blood pressure by 25% within 1-2 hours to avoid serious morbidity or death → this is achieved with IV nitroglycerin (especially if patient has MI) or labetalol. • Or the patient might have complications of end-organ-damage: • Cerebrovascular: TIA, stroke. • Cardiovascular: MI, left ventricular hypertrophy, CHF or aortic aneurysms/dissection. • Retinopathy: hemorrhages, exudates and papilledema (resulting in blurry vision and sometimes blindness). • Renal: microscopic hematuria and elevation of BUN:creatinine.

43. Clinical manifestations (continued): • Secondary HTN (>5% of cases): due to different causes such as (discussed in more details in next slide): • Renovascular disease (renal artery stenosis is the most common cause of secondary HTN). • Cushing disease. • Pheochromocytoma. • Conn syndrome. • Diagnosis of HTN: • If a patient present to the hospital and you find he has high blood pressure with no evidence of end-organ-damage → do not label him as being hypertensive and start him on medications (why?) → because most of these patients have what is known as “white-coat hypertension” as they feel anxious for being in the hospital and seeing doctors. • Let the patient adjust to the environment of the hospital and sit quietly for 5 minutes then measure his blood pressure → usually it will be lower. • Repeat blood pressure measurement 3-6 times over several months before deciding that patient is truly hypertensive. • Management of HTN: • A patient with mild-moderate HTN (blood pressure ≥140/90 mmHg but >160/100 mmHg) should be advised initially to change his lifestyle (e.g. weight loss, physical activity and salt restriction) for 3 months. If after 3 months patient still has a diastolic blood pressure < 90 mmHg → start him on anti-hypertensive (initially diuretics). Add other classes (such as ACE inhibitors) if the patient’s blood pressure is not controlled after a period of time. • A patient with severe HTN (blood pressure ≥160/100 mmHg) must be started initially on 2 medications (e.g. a diuretic and an ACE inhibitor). • Specific hypertensive groups: • Diabetics: ACE inhibitors. • Postmyocardial infarction: β-blockers. • Diminished left-ventricular function: ACE inhibitors and/or β-blockers. • Pregnant patients: methyldopa, hydralazine, labetalol. ACE inhibitors are contraindicated. Hypertension (HTN)

44. Hypertension (HTN)

45. Causes of secondary HTN: • Renal artery stenosis: • Etiology: • Atherosclerotic disease: elderly. • Fibromuscular dysplasia: young females. • Clinical presentation: • Hypertension. • Physical examination: abdominal bruit radiating laterally. • Diagnosis: • Initial: Doppler ultrasound. • Confirmatory: arteriogram. • Treatment: • Initial: percutaneousintraluminal angioplasty. • If it fails → surgical resection. • If both fail or are no possible → ACE inhibitors. • Conn syndrome (primary hyperaldosteronism): • Etiology: • Most commonly: unilateral adrenal adenoma. • Bilateral adrenal hyperplasia. • Clinical manifestations: • Hypertension in association with hypokalemia expressed as muscle weakness or polyuria/polydypsia due to nephrogenic diabetes insipidus. • Diagnosis: • ↑aldosterone in blood and urine. • Abdominal ultrasound or CT. • Treatment: • Unilateral adrenal adenoma: surgical resection. • Bilateral adrenal hyperplasia: potassium-sparing diuretics (e.g. spironolactone). Hypertension (HTN)

46. Causes of secondary HTN (continued): • Pheochromocytoma: • Etiology: • Benign tumor of adrenal medulla. • Rule of 10’s: 10% bilateral, 10% malignant and 10% extra-adrenal. • Clinical manifestations: • Episodic HTN with headache, sweating, palpitations and flushing. • Diagnosis: • VMA, metanephines and free catecholamines in the urine. • Abdominal CT/MRI to localize the tumor. • Treatment: • α-blockers followed by surgical resection of the tumor. • Cushing disease: • Etiology: ↑ACTH production usually from a pituitary adenoma. • Clinical manifestations: HTN + Cushing features: • Truncal obesity + moon-face. • Buffalo hump. • Abdominal striae. • Menstrual irregularities (females); infertility (males). • Diagnosis: • Best initial tests are: 24-hour urinary cortisol; midnight salivary cortisol and low-dose dexamethasonesupression test. • From the tests above, you will know if patient has cushing and whether it from adrenal source (cushing syndrome) or pituitary source (cushing disease) • If the patient has cushing disease, you have to differentiate if it is due to pituitary adenoma or an ectopic tumor by high-dose dexamethasone test. • Treatment: surgical resection of pituitary adenoma when possible. • Coarctation of the aorta: • Definition: it is a narrowing in the aorta usually occurring after the left subclavian artery. • Clinical manifestations: hypertension greater in upper extremities when compared with lower extremities. Hypertension (HTN)

47. Hypertension (HTN)

48. Anti-hypertensive medications: • Diuretics: • Examples: • Thiazides: hydrochlorothiazide. • Loop-diuretics: furosemide. • Potassium-sparing diuretics: spironolactone and amiloride. • Uses: initial choice for hypertension, states of edema and CHF. • Side effects: • ↓ potassium and magnesium. • ↑ calcium, uric acid, glucose and LDL-cholesterol. • Spironolactone: gynecomastia. • Angiotensin Converting Enzyme (ACE) inhibitors: • Examples: they end with (-pril). • Uses: • Diabetics with hypertension to prevent nephropathy. • CHF. • Post-myocardial infarction. • Side effects: cough, neutropenia and hyperkalemia. • Contraindications: • Bilateral renal artery stenosis. • Pregnancy. • Angiotensin receptor antagonists: • Examples: losartan (ending with –sartan). • Indication: used in patients who are intolerant to ACE inhibitors (usually due to cough). • Contraindication: pregnancy. Hypertension (HTN)

49. Anti-hypertensive medications (continued): • Calcium-channel blockers: • Examples: nidedipine (ending with –dipine). • Uses: migraine, angina pectoris, supraventricular arrhythmias, Raynaud’s phenomenon and esophageal spasm. • Side effects: heart block, reflex tachycardia, constipation and peripheral edema. • Contraindications: AV conductions defects and CHF due to systolic dysfunction. • β-blockers: • Examples: atenolol, propranolol, labetolol (ending with –olol). • Uses: • Myocardial Infarction (MI). • CHF due to diastolic dysfunction. • Supraventricular arrhythmias. • Migraine headaches. • Anxiety. • Side effects: • Bronchospasm. • Bradycardia. • Impotence. • Heart block. • Hyperglycemia. • ↓HDL cholesterol and ↑triglycerides. • Contraindications: • Patients with asthma or COPD. • CHF due to systolic dysfunction. • AV conduction defects. Hypertension (HTN)