Respiratory and Renal Pathophysiology Topics in Human Pathophysiology

Respiratory and Renal Pathophysiology Topics in Human Pathophysiology Fall 2011 Gilead Drug Safety and Public Health

Outline Respiratory Disorders Respiratory Interface Lung function Respiratory Disorders Kidneys and Renal Function Overview of system Nephrons Disorders of Urinary System

Figure 10. 8

Figure 10. 7

Selected Respiratory Disorders Viral and bacterial infections fungal infections (Pulmonary aspergillosis) Cystic fibrosis (and accompanying infections) Pneumonia Asthma

Flu • Cause – • Influenza virus Symptoms – – – – Fever Sore throat Cough Body aches Headache Chills Fatigue Vomiting and diarrhea

Flu Susceptible populations Antivirals for influenza – Tamiflu (oseltamivir), Relenza (zanamivir), peramivir Complications Pneumonia and respiratory failure Bronchitis Ear infections Sinus infections

Cystic fibrosis 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 Infections Fungal lung infection - Pulmonary aspergillosis Common with AIDs patients and cystic fibrosis patients Treated with Ambisome (amphoterocin B), one of several antifungals, alters fungal cell permeability

Pulmonary Aspergillosis from an AIDS patient during autopsy http: //www. ispub. com/ostia/index. php? xml. File. Path=journals/ijid/vol 6 n 1/aspergillosis. xml

Pneumonia 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

Pneumonia

Asthma

Gilead treatments for lung infections • Cayston® (aztreonam) for Pseudomonas aeruginosa • Tamiflu for influenza viruses • Ambisome for aspergillus fungus • Vistide for cytomegalovirus

Tests for Lung Function Chest X-ray Pulmonary function tests Sputum cultures Pulse oximetry Arterial Blood Gases (ABGs)

Pneumonia X-ray http: //www. med-ed. virginia. edu/courses/rad/cxr/pathology 3 chest. html

Spirometry

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

Arterial Blood Gases p. H PCO 2 PO 2 Saturation HCO 3 -

Renal Pathophysiology

Kidneys maintain homeostasis Excrete nitrogenous wastes Maintain water balance Regulate salt balance Maintain acid-base balance and blood p. H 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

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

32 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

From: radiology. rsna. org/ content/242/1/175/F 5. expansion

34 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

35 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

Kidneys maintain homeostasis Excrete nitrogenous wastes Maintain water balance Regulate salt balance Maintain acid-base balance and blood p. H Control production of red blood cells Activate an inactive form of vitamin D

Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Increased Normal or GFR 30 -59 GFR m. L/min GFR 6090 m. L/min or 90 m. L/min above GFR 15 -29 m. L/min GFR <15 m. L/min Some evidence of kidney damage (microalbum inuria/protei nuria, hematuria, or histologic changes) Asymptomat ic Kidney damage with severe decrease in GFR Hyperkalemia Anemia 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 Kidney damage with mild decrease in GFR Asympto matic Kidney damage with moderate decrease in GFR Asymptomatic, may have anemia 37

Treatment for Renal Failure Control the underlying cause, i. e. diabetes, HTN, drug therapy Controlled fluid intake Diet rh. EPO Kidney Transplant Dialysis

Dialysis Treatment

40 Clinical Tests for Renal Function Complete medical and medication history Complete physical examination Microscopic exam---clues in the urine sediment (eg. hematuria) Urinalysis---any protein, WBCs, blood? BUN and creatinine, electrolytes, GFR, quantitative protein, urine and serum potassium Renal ultrasound Renal biopsy

Topics in Human Pathophysiology Fall 2011 Gilead Drug Safety and Public Health Thank You!