 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

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

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 Flu

 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. Cystic fibrosis

 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 Fungal Lung Infections

Pulmonary Aspergillosis from an AIDS patient during autopsy 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 Pneumonia

Asthma

Gilead treatments for lung infections 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) Tests for Lung Function

Pneumonia X-ray

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

 pH  PCO 2  PO 2  O 2 Saturation  HCO 3 - Arterial Blood Gases

Renal Pathophysiology

Kidneys maintain homeostasis  Excrete nitrogenous wastes  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

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 32

From: radiology.rsna.org/ content/242/1/175/F5.expansion

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 34 Acute Renal Failure

 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 35 Kidney Disorders Kidney Disorders Chronic Renal Failure - End Stage Renal Disease (ESRD

Kidneys maintain homeostasis  Excrete nitrogenous wastes  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

37 Stage 1Stage 2Stage 3Stage 4Stage 5 Increased GFR 90mL/min or above Normal or GFR mL/min GFR mL/min GFR mL/min GFR <15 mL/min Some evidence of kidney damage (microalbum inuria/protei nuria, hematuria, or histologic changes) Asymptomat ic Kidney damage with mild decrease in GFR Asympto matic Kidney damage with moderate decrease in GFR Asymptomatic, may have anemia Kidney damage with severe decrease in GFR Hyperkalemi a 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

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

Dialysis Treatment

 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 40 Clinical Tests for Renal Function

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