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

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)

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  PCO 2  PO 2  O 2 Saturation  HCO 3 -

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.

Figure Tubules reabsorb nonwastes, and secrete wastes, allow urine to be concentrated, control electrolyte balance.

Kidney Disorders 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 changesTests – Urinalysis – Serum creatinine – blood urea nitrogen (BUN) – serum potassium – Kidney ultrasound or X- ray to rule out obstructions to urine 30

Kidney Disorders 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) 33 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 mL/min Kidney damage with mild decrease in GFR Asymptomatic Stage 3 GFR mL/min Kidney damage with moderate decrease in GFR Asymptomatic, may have anemia Stage 4 GFR 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 retention  edema, pulmonary hypertension, systolic hypertension

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