Renal

Renal System Overview

  • Lecture by Dr. Karel Alcedo for PHCY 412: Human Physiology/Pathophysiology II (Spring 2026)

Renal Function

Filtration

  • Blood filtration occurs in the glomerulus.

  • Filtration size cutoff: Approximately 70 kDa.

  • Glomerular basement membrane: Negatively charged, filtering out negatively charged proteins.

  • Filtrate composition includes:
      - H2O
      - Ions:
        - Sodium (Na+Na^+)
        - Chloride (Cl−Cl^-)
        - Potassium (K+K^+)
        - Phosphate (PO43−PO_4^{3-})
        - Bicarbonate (HCO3−HCO_3^-)
      - Small proteins (e.g., insulin, hemoglobin)
      - Molecules such as lipids, amino acids, glucose, among others.
      - Metabolic waste products such as:
        - Creatinine from muscle metabolism
        - Urea from protein metabolism
        - Uric acid

Re-absorption

  • Approximately 99% of glomerular filtrate is reabsorbed in renal tubules.

  • Major sites of reabsorption:
      - Proximal tubule: Reabsorbs the majority of the filtrate.
      - Loop of Henle:
        - Descending limb: Reabsorbs H2O.
        - Ascending limb: Secretes Sodium (Na+Na^+) into the medullary interstitium, crucial for water conservation.
      - Distal tubule:
        - Fine-tunes water and electrolyte balance by reabsorbing Sodium (Na+Na^+) and secreting Potassium (K+K^+).
        - Regulates Calcium (Ca2+Ca^{2+}) and Magnesium (Mg2+Mg^{2+}).

Excretion

  • Collecting duct: Responsible for fine-tuning urine concentration with respect to:
      - Sodium (Na+Na^+) and H2O
      - Urea

  • Regulation by hormones:
      - ADH (Vasopressin): Promotes water retention.
      - Aldosterone: Promotes sodium (Na+Na^+) and water retention.
      - Atrial Natriuretic Peptide (ANP): Promotes sodium (Na+Na^+) and water excretion.

  • Collects urine for excretion through the renal pelvis.

Dysfunction of the Nephrons

  • Causes include:
      - Acute kidney injury (AKI):
        - Prerenal: Related to blood flow issues.
        - Intrinsic: Damage to the kidney tissue.
        - Postrenal: Obstruction in the urinary flow.
      - Chronic kidney disease (CKD): Characterized by a decrease in GFR lasting longer than 3 months, leading to fluid, waste, and electrolyte accumulation.

Chronic Kidney Disease (CKD)

Definition

  • Defined by structural or functional abnormalities in the kidney present for 3 months or longer.

  • Symptoms include:
      - Lower glomerular filtration rate (GFR)
      - Higher urinary albumin-to-creatinine ratio (ACR)

Important Markers

  • Creatinine: Excreted at a constant rate, while Albumin remains in the blood under normal physiological conditions.

  • Kidney Disease: Improving Global Outcomes (KDIGO): Classification by cause, GFR, and albuminuria.

CKD Epidemiology & Etiology

  • Approximately 30 million adults in the U.S., with a prevalence of 1 in 7 adults.

  • Etiological factors include:
      - Diabetes mellitus
      - Hypertension
      - Polycystic kidney disease
      - Infections
      - Renal artery stenosis
      - Drug-induced kidney disease.

Pathophysiology of CKD

  • Effects of Diabetes mellitus on kidneys include:
      - Formation of advanced glycation end products.
      - Increased glomerular blood flow leading to glomerular hypertrophy.

  • Initial pathogenic injury can lead to:
      - Glomerular injury and reduced filtration area.
      - Adaptive hemodynamic changes and epithelial injury, including focal detachment of epithelial foot processes.

  • Consequences include:
      - Increased glomerular capillary pressure, leading to proteinuria.
      - Arteriosclerosis, hyperlipidemia, mesangial injury, and glomerulosclerosis.

  • Progression can be compounded by the formation of microaneurysms and systemic hypertension.

CKD Clinical Manifestations

Na+/H2O Balance

  • Retention leads to:
      - Symptoms: hypertension, peripheral edema, weight gain.

  • Impairment leads to:
      - Increased sensitivity to sudden extrarenal Na+/H2O losses such as vomiting and diarrhea, resulting in extra cellular fluid (ECF) depletion.

  • Symptoms include:
      - Dry mucous membranes, tachycardia, hypotension, dizziness, vascular collapse, and potential shock.

K+ Balance

  • GFR < 15 mL/min causes hyperkalemia, a potentially life-threatening complication.

  • Compensatory mechanism involves aldosterone-mediated K+ transport in the distal tubule.

  • CKD patients' inability to compensate for GFR results in difficulty excreting K+.

  • Increased risk of hyperkalemia from endogenous (e.g., hemolysis, infection) and exogenous (e.g., potassium-rich foods, blood transfusions, medications) sources.

  • Symptoms include:
      - Muscle weakness, fatigue, nausea, numbness/tingling, heart palpitations, and arrhythmias.

Mineral & Bone Metabolism

  • Disorders of phosphate (PO43−PO_4^{3-}), calcium (Ca2+Ca^{2+}), and bone metabolism occur due to:
      - Diminished calcium absorption from the gut.
      - Secondary hyperparathyroidism.
      - Disordered vitamin D metabolism.
      - Retention of phosphorus due to chronic metabolic acidosis.

  • Symptoms include:
      - Enhanced bone resorption, osteomalacia.

Hematologic Abnormalities

  • Abnormalities include:
      - Altered RBC count, WBC function, and clotting.

  • Primary cause: reduced erythropoietin production leading to impaired erythropoiesis.

  • Other causes: uremic toxins, bone marrow fibrosis, dialysis-associated hemolysis, aluminum toxicity.

  • Symptoms include:
      - Bruising, clotting issues, spontaneous GI and cerebrovascular hemorrhage (including hemorrhagic stroke and subdural hematoma).

  • Laboratory findings:
      - Prolonged bleeding time, abnormal platelet aggregation, impaired prothrombin consumption.
      - Increased risk of infections due to WBC suppression from uremic toxins, acidosis, and malnutrition.

Cardiovascular and Pulmonary Complications

  • Leading cause of mortality in CKD patients:
      - Hypertension stemming from Na+/H2O retention and hyperreninemia.
      - Uremic toxins can lead to pericarditis, though this complication is less common due to dialysis.

  • Symptoms include:
      - Hypertension, hyperlipidemia, glucose intolerance, increased cardiac output, myocardial infarction, stroke, peripheral vascular disease.

Neuromuscular Abnormalities

  • Uremia results in:
      - Symptoms: sleep disturbances, impaired mental concentration, memory loss, judgment errors, neuromuscular irritability (e.g., hiccups, cramps, twitching), progressing to serious conditions like asterixis, myoclonus, stupor, seizures, and coma in end-stage uremia.
      - Peripheral neuropathy presenting as restless legs syndrome.

Endocrine & Metabolic Abnormalities

  • Uremia impacts:
      - Estrogen levels in women leading to amenorrhea, decreased fertility, and pregnancy challenges.
      - Testosterone levels in men leading to impotence, oligospermia, and germinal cell dysplasia.
      - Insulin degradation, increasing hyperglycemic patients' responses to insulin.

  • Skin abnormalities include:
      - Pallor due to anemia, color changes from pigmented metabolites, ecchymoses due to clotting issues, pruritus due to calcium deposits from hyperparathyroidism.

Metabolic Acidosis

  • Caused by impaired acid excretion and bicarbonate (HCO3−HCO_3^-) generation.

  • CKD patients are particularly susceptible to acidosis from sudden acid loads or bicarbonate loss.

  • Symptoms include:
      - Kussmaul breathing, nausea/vomiting, fatigue, headaches, confusion.
      - Untreated cases may lead to cardiac arrhythmias, stupor, coma, or death.

Gastrointestinal Abnormalities

  • Non-specific gastrointestinal symptoms commonly observed:
      - Anorexia, hiccups, nausea, vomiting.
      - Symptoms tend to improve with dialysis.