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Gilead -Topics in Human Pathophysiology Fall 2010 Drug Safety and Public Health Gas exchange Protection Speech Compression of abdomen and spine stiffening Acid-Base balance Flu (example H1N1) Asthma Cystic fibrosis (and accompanying infections) Pulmonary aspergillosis Pneumonia • Cause – Influenza virus • Symptoms – Fever – Sore throat – Cough – Body aches – Headache – Chills – Fatigue – Vomiting and diarrhea Susceptible populations Antivirals for influenza – Tamiflu (oseltamivir), Relenza (zanamivir), peramivir Complications ◦ ◦ ◦ ◦ Pneumonia and respiratory failure Bronchitis Ear infections Sinus infections Inherited disorder causing a defect in a cell membrane Cl- channel Causes thick sticky mucus buildup in airways and ducts of pancreas, etc. Shortens lifespan because of pneumonia, malnutrition, etc. Fungal lung infection Common with AIDs patients and cystic fibrosis patients Treated with Ambisome (amphoterocin B), one of several antifungals, alters fungal cell permeability http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijid/vol 6n1/aspergillosis.xml Fluid buildup in lung alveoli Thickens respiratory interface, interrupting diffusion of gases Caused by a wide variety of microorganisms including bacteria, aspergillus and pneumocystis fungi, influenza virus (Tamiflu), cytomegalovirus (Vistide) • Cayston® (aztreonam) for Pseudomonas aeruginosa • Tamiflu for influenza viruses • Ambisome for aspergillus fungus • Vistide for cytomegalovirus Chest X-ray Pulmonary function tests Sputum cultures Pulse oximetry Arterial Blood Gases (ABGs) http://www.med-ed.virginia.edu/courses/rad/cxr/pathology3chest.html Sputum Culture •Patient donates a sputum sample •It is cultured with various media to determine causative agent of lung infection Pulse Oximetry •Measures arterial hemoglobin oxygen saturation •Normal is > 95% •Indicator of effectiveness of respiratory interface and gas diffusion pH PCO2 PO2 O2 Saturation HCO3- Renal Pathophysiology Kidneys maintain homeostasis • • • • • Maintain water balance Regulate salt balance Maintain acid-base balance and blood pH Control production of red blood cells Activate an inactive form of vitamin D Figure 15.2 Normal Kidney Anatomy The nephron is the functional unit of the kidney Figure 15.6 Overview of Nephron Actions Nephron Actions • Filtration • Reabsorption • Secretion Figure 15.4 Glomerular Apparatus The glomerular capillaries filter the blood. Glomerular filtration rate is an indicator of kidney health. Tubules reabsorb nonwastes, and secrete wastes, allow urine to be concentrated, control electrolyte balance. Figure 25.16 Kidney Disorders Acute Renal Failure • Causes: – – – – – – Decreased blood flow to kidneys Large kidney stones Infections Burns Severe injuries Toxic drugs and or chemicals (antivirals, especially anti-HIV drugs) • Tubule damage is typical and signs include problems with reabsorption and secretion and thus changes in serum electrolytes • Can be reversed by eliminating the cause 28 From: radiology.rsna.org/ content/242/1/175/F5.expansion Acute Renal Failure Signs & symptoms – Oliguria or anuria – Swelling / edema – Mental status changes Tests – Urinalysis – Serum creatinine – blood urea nitrogen (BUN) – serum potassium – Kidney ultrasound or Xray to rule out obstructions to urine 30 Kidney Disorders Chronic Renal Failure - End Stage Renal Disease (ESRD) • Generally caused by long term damage to nephrons reducing GFR and urine output • Risks include hypertension, diabetes mellitus, untreated acute renal failure • Increased leakage through glomerulus leads to – Proteinuria- proteins in urine – Hematuria – blood in urine – Azotemia – excess nitrogen containing compounds in blood – Edema – Hypertension 31 Kidneys maintain homeostasis • • • • • Maintain water balance Regulate salt balance Maintain acid-base balance and blood pH Control production of red blood cells Activate an inactive form of vitamin D Stages of Chronic Kidney Disease (ESRF) Stage 1 Normal or increased GFR 90mL/min or above Some evidence of kidney damage (microalbuminuria/proteinuria, hematuria, or histologic changes) Asymptomatic Stage 2 GFR 60-90 mL/min Kidney damage with mild decrease in GFR Asymptomatic Stage 3 GFR 30-59 mL/min Kidney damage with moderate decrease in GFR Asymptomatic, may have anemia Stage 4 GFR 15-29 mL/min Kidney damage with severe decrease in GFR Hyperkalemia Anemia Stage 5 GFR <15 mL/min Kidney failure; renal replacement therapy needed to sustain life Uremia, platelet dysfunction, encephalopathy, peripheral neuropathy, anorexia, nausea and vomiting, pericarditis, pruritus, lethargy and increased somnolence) Metabolic acidosis Protein catabolism Renal bone disease Sodium & water retentionedema, pulmonary hypertension, systolic hypertension 33 Treatment for Renal Failure • Control the underlying cause, i.e. diabetes, HTN, drug therapy • Controlled fluid intake • Diet • rhEPO • Kidney Transplant • Dialysis Dialysis Treatment Review of Clinical Tests for Renal Injury • Complete medical and medication history • Complete physical examination • Microscopic exam---clues in the urine sediment (eg. hematuria) • Urinalysis---any protein, WBCs, blood? • BUN/creatinine, electrolytes, GFR, quantitative protein, urine serum/potassium • Renal ultrasound • Renal biopsy 36
