10.2 Clinical Pathophysiology: Respiratory, GI, Renal, and Other Systems

Respiratory Pathophysiology

Asthma

Asthma is a chronic inflammatory airway disease with Th2-mediated eosinophilic inflammation, bronchoconstriction, mucous hypersecretion, and airway remodeling. Triggers (allergens, exercise, infection, irritants) produce bronchospasm, wheeze, dyspnea, cough. GINA classification (Global Initiative for Asthma) stratifies treatment Steps 1-5 by symptom control and medication intensity — short-acting beta-agonist (SABA) reliever plus inhaled corticosteroid (ICS) controller is the foundation; biologics (omalizumab, mepolizumab, dupilumab) target severe eosinophilic or allergic phenotypes.

COPD

Chronic Obstructive Pulmonary Disease (COPD) features persistent airflow limitation. Emphysema reflects protease-antiprotease imbalance — neutrophil elastase overwhelms alpha-1 antitrypsin, destroying alveolar walls. Chronic bronchitis features chronic productive cough with mucous gland hyperplasia. GOLD classification (Global Initiative for Chronic Obstructive Lung Disease) assigns Groups A-D based on symptoms (mMRC, CAT score) and exacerbation risk; LAMA, LABA, and ICS/LABA combinations form the pharmacologic backbone.

Pneumonia, Pulmonary Embolism, Pulmonary Hypertension

Pneumonia: alveolar infection drives neutrophil exudate and impaired gas exchange; typical (pneumococcal) vs atypical (Mycoplasma, Legionella) patterns. Pulmonary embolism: see Virchow's triad. Pulmonary hypertension: elevated pulmonary arterial pressure with right heart strain (cor pulmonale).

Gastrointestinal Pathophysiology

GERD

Gastroesophageal reflux disease (GERD) — lower esophageal sphincter (LES) dysfunction permits acid reflux; complications include esophagitis, stricture, Barrett's esophagus (intestinal metaplasia, premalignant), and esophageal adenocarcinoma.

Peptic Ulcer Disease

Peptic ulcer disease (PUD) — Helicobacter pylori infection and NSAID use are the dominant causes. H. pylori urease enables survival in acid and induces mucosal inflammation; NSAIDs inhibit COX-1, depleting protective prostaglandins and mucus. Zollinger-Ellison syndrome (gastrin-secreting tumor) causes refractory multiple ulcers.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) comprises Crohn's disease (transmural inflammation, skip lesions, any GI segment) and ulcerative colitis (mucosal inflammation, continuous from rectum). Immune dysregulation with TNF-alpha, IL-12/23 drives chronic inflammation; biologics (infliximab, adalimumab, ustekinumab, vedolizumab) target these cytokines.

IBS, Liver Disease, Pancreatitis

Irritable bowel syndrome (IBS) is a functional disorder (no inflammation) with pain related to defecation and altered bowel habit (Bristol scale). Cirrhosis — fibrosis and nodular regeneration from chronic injury (Hepatitis B/C, alcohol, NAFLD); portal hypertension produces varices, ascites, splenomegaly; hepatic encephalopathy arises when ammonia and other neurotoxins cross the blood-brain barrier. Pancreatitis features premature zymogen activation, autodigestion, and systemic inflammatory response.

Renal Pathophysiology

Acute Kidney Injury

Acute kidney injury (AKI) is classified as prerenal (decreased renal perfusion — hypovolemia, heart failure, sepsis), intrinsic (acute tubular necrosis (ATN) from ischemia or nephrotoxins such as contrast, aminoglycosides, cisplatin; acute interstitial nephritis (AIN) from allergic drug reaction — beta-lactams, NSAIDs, PPIs), or postrenal (urinary obstruction — BPH, stones, tumor).

Chronic Kidney Disease

Chronic kidney disease (CKD) is progressive nephron loss over ≥3 months. Complications: anemia (reduced erythropoietin), chronic kidney disease-mineral and bone disorder (CKD-MBD) — phosphate retention, reduced calcitriol, secondary hyperparathyroidism, renal osteodystrophy; hyperkalemia, metabolic acidosis, fluid overload, uremic symptoms, accelerated cardiovascular disease.

Nephrotic vs Nephritic Syndromes

Nephrotic syndrome: heavy proteinuria (>3.5 g/day), hypoalbuminemia, edema, hyperlipidemia — minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis. Nephritic syndrome: hematuria, hypertension, mild proteinuria, azotemia — post-streptococcal glomerulonephritis, IgA nephropathy, rapidly progressive GN.

Other Systems

Neurologic

Stroke — ischemic (thrombotic or embolic occlusion, ~85% of cases) vs hemorrhagic (intracerebral, subarachnoid). Seizure disorders — focal vs generalized, from abnormal synchronous neuronal discharge; etiologies include structural, metabolic, infectious, genetic. Parkinson's disease — degeneration of dopaminergic neurons in the substantia nigra pars compacta producing bradykinesia, rigidity, resting tremor, postural instability. Alzheimer's disease — amyloid-beta plaques, tau neurofibrillary tangles, and cholinergic deficit producing progressive memory and cognitive decline.

Rheumatologic

Rheumatoid arthritis (RA) — autoimmune synovitis with anti-cyclic citrullinated peptide (anti-CCP) antibodies and joint destruction; treated with DMARDs (methotrexate), biologics (anti-TNF, anti-IL6), JAK inhibitors. Osteoarthritis — mechanical cartilage degradation with secondary inflammation. Gout — monosodium urate crystal deposition in joints; acute (NSAIDs, colchicine, glucocorticoids) vs chronic (allopurinol, febuxostat, pegloticase). Systemic lupus erythematosus (SLE) — multi-system autoimmunity with ANA, anti-dsDNA, anti-Smith antibodies; nephritis, malar rash, photosensitivity.

Infectious Disease and Sepsis

Sepsis is a dysregulated host response to infection causing vasodilation, capillary leak, disseminated intravascular coagulation (DIC), and multi-organ dysfunction. The qSOFA score (RR ≥22, altered mentation, SBP ≤100) screens for likely septic patients outside the ICU; lactate ≥2 mmol/L reflects tissue hypoperfusion and guides fluid resuscitation. Septic shock is sepsis with persistent hypotension requiring vasopressors despite adequate volume, with mortality exceeding 30%. Common infections by system: respiratory (pneumococcal, influenza, COVID), genitourinary (UTI, pyelonephritis), gastrointestinal (C. difficile, Salmonella, Campylobacter), skin and soft tissue (cellulitis, S. aureus, streptococcus), bloodstream (endocarditis, central line infection). Early antibiotics (within 1 hour of recognition), source control, and hemodynamic support with crystalloids and norepinephrine are foundational; vancomycin plus piperacillin-tazobactam is a common empiric broad regimen pending cultures.