Unit 6: Renin–Angiotensin–Aldosterone System (RAAS)
Purpose and Physiological Importance
The Renin–Angiotensin–Aldosterone System (RAAS) is a crucial hormonal pathway responsible for regulating systemic blood pressure, maintaining extracellular fluid balance, and managing electrolyte homeostasis. It primarily activates as a compensatory mechanism in response to decreased renal perfusion, low arterial pressure, or reduced sodium concentration. Through this response, RAAS helps restore hemodynamic stability and supports overall homeostasis within the body.
What Stimulates RAAS Activation?
RAAS activation is triggered by the kidneys sensing certain physiological changes, including:
A drop in arterial blood pressure
Reduced sodium delivery to the distal renal tubules
Decreased circulating blood volume
These signals promote sodium and water retention, aiding in restoring adequate blood pressure and improving tissue perfusion.
Stepwise Mechanism of RAAS Activation
| Step | Organ/Site | Action |
|---|---|---|
| 1 | Liver | Produces and releases angiotensinogen into the bloodstream |
| 2 | Kidney (juxtaglomerular cells) | Secretes renin in response to low renal perfusion |
| 3 | Blood | Renin converts angiotensinogen to angiotensin I |
| 4 | Lungs (pulmonary endothelium) | Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II |
| 5 | Adrenal cortex | Releases aldosterone stimulated by angiotensin II |
| 6 | Kidneys and blood vessels | Aldosterone promotes sodium retention; angiotensin II causes vasoconstriction |
Physiological Effects of Angiotensin II
Angiotensin II, the principal effector hormone of RAAS, exerts several important effects:
Stimulates aldosterone secretion, increasing sodium and water reabsorption in the kidneys
Enhances potassium excretion to maintain electrolyte balance
Induces arteriolar vasoconstriction, raising systemic vascular resistance and blood pressure
Acute Pyelonephritis
What Is Acute Pyelonephritis?
Acute pyelonephritis is an infection involving one or both kidneys, targeting the renal pelvis, calyces, interstitial tissue, and renal tubules. It represents a severe upper urinary tract infection that can cause substantial kidney damage if untreated.
Who Is at Risk?
Individuals with the following risk factors are more susceptible:
Urinary tract obstructions (e.g., stones or strictures)
Vesicoureteral reflux, especially in children
Female anatomy, which facilitates ascending infections
Which Microorganisms Cause Acute Pyelonephritis?
Common causative bacteria ascend from the lower urinary tract, primarily:
Escherichia coli (most frequent)
Proteus species
Pseudomonas aeruginosa
What Are the Pathological Changes?
Infection predominantly damages renal tubules, resulting in:
Fibrosis and scarring due to ongoing inflammation
Tubular atrophy from repeated injury
Permanent loss of functioning renal tissue following recurrent infections
What Are the Clinical Symptoms?
Typical signs and symptoms include:
High fever with chills
Flank or groin pain
Dysuria and frequent urination
Costovertebral angle tenderness
Older adults may present atypically with fatigue or low-grade fever rather than classic symptoms.
How Is It Diagnosed and Treated?
Diagnosis involves urinalysis and urine cultures, with white blood cell casts indicating renal involvement. Blood cultures and imaging may be necessary for complicated cases. Treatment requires targeted antibiotics over 2 to 3 weeks, with follow-up cultures if symptoms persist or recur.
Acute Glomerulonephritis
What Is Acute Glomerulonephritis?
This condition is defined by inflammation and injury to the kidney’s glomeruli. It may be a primary renal disorder or secondary to systemic diseases.
What Causes It?
Common causes include:
Immune-mediated responses (e.g., post-infectious)
Infectious agents
Ischemic injury
Exposure to toxins or drugs
Vascular diseases
How Does It Affect the Kidney?
Inflammation damages the glomerular filtration barrier—comprising endothelial cells, basement membrane, and podocytes—leading to impaired filtration and progressive nephron loss.
What Is the Clinical Course?
Symptoms may develop slowly, causing significant renal injury before diagnosis. Severe cases may exhibit oliguria (reduced urine output) and rapid deterioration of kidney function.
Diabetes Insipidus: Diagnosis and Management
How Is Diabetes Insipidus Diagnosed?
| Type of DI | Response to Desmopressin (ADH analog) |
|---|---|
| Neurogenic (central) | Increase in urine osmolality |
| Nephrogenic | No significant change in urine osmolality |
What Are the Treatment Approaches?
Neurogenic DI:
Administer desmopressin orally, nasally, or intravenously to replace ADH
Treat underlying causes such as trauma or tumors
Nephrogenic DI:
Discontinue offending drugs (e.g., lithium)
Maintain hydration and correct electrolyte imbalances
Use thiazide diuretics to reduce urine output
Implement dietary sodium and protein restrictions
Gastroesophageal Reflux Disease (GERD)
What Is GERD?
GERD is a chronic disorder characterized by reflux of acidic gastric contents into the esophagus, causing mucosal injury and inflammation.
How Does GERD Develop?
It results mainly from the failure of the lower esophageal sphincter (LES) to maintain adequate tone, permitting acid and pepsin reflux. This may be due to transient LES relaxations or structural weakness.
What Factors Worsen GERD?
Increased intra-abdominal pressure caused by obesity, pregnancy, coughing, vomiting, or heavy lifting exacerbates reflux.
What Are the Common Symptoms?
Heartburn and epigastric discomfort after meals
Chronic cough and hoarseness
Exacerbations of asthma and sinus infections
How Is GERD Diagnosed?
Upper endoscopy with biopsy assesses mucosal damage and excludes premalignant conditions such as Barrett’s esophagus.
What Treatments Are Available?
| Treatment Category | Description |
|---|---|
| First-line | Proton pump inhibitors (e.g., omeprazole) |
| Second-line | H2 receptor antagonists (e.g., famotidine) |
| Adjunctive | Antacids, prokinetics |
| Lifestyle | Weight loss, dietary modifications, bed elevation |
| Surgical | Laparoscopic fundoplication for refractory cases |
Glomerulonephritis Overview
What Is Glomerulonephritis?
A group of inflammatory kidney disorders targeting glomeruli, resulting in impaired filtration and fluid regulation.
Types and Causes
| Type | Features | Common Causes |
|---|---|---|
| Acute | Sudden onset, often post-infectious | Infections, autoimmune diseases, toxins |
| Chronic | Progressive, leads to chronic kidney disease (CKD) | Hypertension, diabetes, genetic factors, malignancies |
Clinical Features
Acute: hematuria, edema, hypertension
Chronic: proteinuria, nocturia, fatigue, generalized edema
Diagnosis and Management
Diagnosis includes lab tests, imaging, and renal biopsy. Treatment varies from antibiotics to immunosuppressants, alongside blood pressure control and dietary management. Advanced cases may require dialysis or kidney transplantation.
Nephrotic Syndrome
Definition and Characteristics
Nephrotic syndrome is identified by heavy proteinuria (>3.5 g/day), hypoalbuminemia, generalized edema, and hyperlipidemia.
Pathophysiology
Damage to the glomerular filtration barrier increases permeability to proteins, causing albumin loss, decreased plasma oncotic pressure, fluid shift into tissues, and activation of RAAS, which exacerbates edema.
Types and Causes
Primary: Minimal change disease, focal segmental glomerulosclerosis
Secondary: Diabetes, amyloidosis, infections, systemic diseases
Complications
Patients are at increased risk for infections, thromboembolism, malnutrition, and cardiovascular diseases.
Management Strategies
| Aspect | Recommendations |
|---|---|
| Dietary Management | Balanced protein intake, sodium restriction, controlled calories |
| Pharmacologic Therapy | Corticosteroids (e.g., prednisone), immunosuppressants (cyclophosphamide, cyclosporine), diuretics, ACE inhibitors, and ARBs |
| Complication Management | Blood pressure control (nifedipine, hydralazine, beta-blockers), thrombosis prevention, infection prophylaxis, IV albumin for hypovolemia |
Peptic Ulcer Disease (PUD) Overview
What Is PUD?
Peptic ulcer disease involves mucosal erosions or ulcers in the esophagus, stomach, or duodenum caused by acid and pepsin damage.
Risk Factors
Helicobacter pylori infection
Chronic NSAID or aspirin use
Smoking, alcohol consumption
Chronic illnesses, obesity, advanced age, genetics
Types and Symptoms
| Ulcer Type | Location | Symptoms |
|---|---|---|
| Gastric | Stomach | Pain worsens after eating, weight loss, early satiety |
| Duodenal | Duodenum | Pain relieved by food, often nocturnal |
| Esophageal | Esophagus | GERD symptoms, dysphagia |
Diagnosis
Upper GI endoscopy with biopsy, H. pylori testing (biopsy or stool antigen), and blood tests for anemia.
Treatment
| Condition | Approach |
|---|---|
| H. pylori-positive | Clarithromycin-based triple therapy or bismuth quadruple therapy with PPIs |
| H. pylori-negative | Proton pump inhibitors for 6–8 weeks, avoidance of NSAIDs |
| Lifestyle | Avoid NSAIDs, alcohol, smoking; surgery for refractory cases |
Overview of Pyelonephritis
What Is Pyelonephritis?
An infection of the renal pelvis, calyces, and interstitial tissue, presenting acutely with systemic symptoms or chronically due to recurrent infections causing scarring.
Causes and Progression
Predominantly caused by E. coli, followed by Proteus and Pseudomonas. Acute infections cause inflammation and purulent urine; chronic infection results in fibrosis and impaired renal concentration.
Clinical Features
Acute: fever, chills, flank pain, urinary symptoms
Chronic: hypertension, renal failure, metabolic imbalances
Diagnosis and Treatment
Urinalysis and culture confirm infection; imaging assists in chronic cases. Treatment requires prolonged antibiotics and correction of anatomical abnormalities.
Renin–Angiotensin–Aldosterone System (RAAS) Summary
| Step | Organ/Site | Action |
|---|---|---|
| 1 | Liver | Releases angiotensinogen |
| 2 | Kidney | Renin converts angiotensinogen to angiotensin I |
| 3 | Lungs | ACE converts angiotensin I to angiotensin II |
| 4 | Adrenal cortex | Aldosterone secretion |
| 5 | Kidneys & vessels | Sodium retention and vasoconstriction |
ACE inhibitors and ARBs are key therapeutic agents to interrupt this cascade, particularly in hypertension and kidney disease management.
Renal Calculi (Kidney Stones)
Overview and Formation
Renal calculi are crystalline aggregates forming in supersaturated urine, influenced by factors like supersaturation, crystal nucleation, growth, and insufficient inhibitors such as citrate.
Relationship Between Urine pH and Stone Type
| Urine pH | Stone Type |
|---|---|
| >7.0 | Calcium phosphate |
| <5.0 | Uric acid |
Management and Prevention
Treatment includes pain relief, hydration, and facilitating stone passage. Large stones may require lithotripsy or surgery. Prevention focuses on increasing fluid intake, restricting sodium, moderating animal protein, and maintaining balanced calcium consumption.
Renal Failure Overview
Acute vs. Chronic
Renal failure occurs due to impaired filtration and fluid/electrolyte imbalance. Acute renal failure may be prerenal, intrarenal, or postrenal, while chronic kidney disease is progressive and irreversible.
Dialysis Modalities
Hemodialysis and continuous renal replacement therapies effectively remove waste and fluids but do not restore kidney function.
Urinary Tract Infections (UTIs)
What Are UTIs?
UTIs are bacterial infections of the urinary tract, with Escherichia coli being the most common pathogen.
Risk Factors
Sexual activity, pregnancy, menopause, urinary obstruction, and hygiene practices influence risk.
Clinical Presentation and Management
Cystitis: dysuria, urgency, suprapubic pain
Pyelonephritis: systemic symptoms including fever and flank pain
Diagnosis relies on urinalysis and culture. Treatment involves appropriate antibiotics, hydration, and preventive strategies.
References
Centers for Disease Control and Prevention. (2023). Urinary tract infection (UTI). https://www.cdc.gov
Feldman, M., Friedman, L. S., & Brandt, L. J. (2021). Sleisenger and Fordtran’s gastrointestinal and liver disease (11th ed.). Elsevier.
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Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (2022). Harrison’s principles of internal medicine (21st ed.). McGraw-Hill.
Kumar, V., Abbas, A. K., & Aster, J. C. (2020). Robbins and Cotran pathologic basis of disease (10th ed.). Elsevier.
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). Elsevier.
National Institute of Diabetes and Digestive and Kidney Diseases. (2023). Kidney disease and renal failure. https://www.niddk.nih.gov
Sung, J. J. Y., Kuipers, E. J., & El-Serag, H. B. (2020). Systematic review: The global incidence and prevalence of peptic ulcer disease. Alimentary Pharmacology & Therapeutics, 29(9), 938–946.
UpToDate. (2024). Management of nephrotic syndrome, pyelonephritis, and renal calculi. Wolters Kluwer.