Chronic Kidney Injury Midterm Notes PDF

6 1 URINARY AND RENAL DISORDERS – Chronic Kidney Disease Chronic Kidney Disease (CKD) Chronic Kidney Disease (CKD) is defined as a progressive and irreversible loss of kidney func:on. It is characterized by...

6 1 URINARY AND RENAL DISORDERS – Chronic Kidney Disease Chronic Kidney Disease (CKD) Chronic Kidney Disease (CKD) is defined as a progressive and irreversible loss of kidney func:on. It is characterized by a glomerular filtra:on rate (GFR) of less than 60 mL/min/1.73 m² for three or more months and affects every body system if le> untreated. 1. Most Likely Cause The most common causes of CKD include: Diabetes Mellitus (Diabe:c Nephropathy): Chronic hyperglycemia leads to injury of the glomerular capillaries due to the deposiEon of advanced glyca:on end-products (AGEs), causing inflammaEon, fibrosis, and eventual loss of nephrons. Hypertension (Hypertensive Nephropathy): High blood pressure causes glomerular hypertension, promoEng vascular sclerosis, which damages the nephron's filtering capacity. Glomerulonephri:s: InflammaEon of the glomeruli damages the filtraEon system, which can lead to chronic kidney disease over Eme. Polycys:c Kidney Disease (PKD): A geneEc disorder characterized by the growth of numerous fluid-filled cysts in the kidneys that gradually replace normal kidney Essue. Autoimmune Diseases: CondiEons such as Systemic Lupus Erythematosus (SLE) can lead to glomerular injury, eventually leading to CKD. 2. Pathophysiology The pathophysiology of CKD involves progressive nephron loss and adaptaEons of the surviving nephrons that ulEmately become maladapEve. 1. Loss of Func:onal Nephrons: o Injury to nephrons due to hypertension, diabetes, or immune response causes the loss of funcEonal nephron units. o The remaining nephrons compensate by increasing their filtraEon rate, a process called glomerular hyperfiltra:on. 2. Hyperfiltra:on Injury: o Over Eme, increased glomerular capillary pressure damages the endothelial cells, leading to podocyte detachment and thickening of the glomerular basement membrane (GBM). o This process leads to proteinuria, which contributes to tubulointers::al inflamma:on and fibrosis. 3. Tubulointers::al Inflamma:on: o FiltraEon of excessive proteins and acEvaEon of tubular cells induce the producEon of inflammatory cytokines. o These cytokines promote fibrosis, angiotensin II upregula:on, and increased producEon of reac:ve oxygen species (ROS), which further injure nephron structures. 4. Fibrosis and Scarring:  2 oChronic injury triggers the producEon of myofibroblasts, which deposit extracellular matrix proteins (collagen), leading to scarring. o This process results in the replacement of normal kidney Essue with fibro:c :ssue, reducing kidney funcEon. 5. Reduced Glomerular Filtra:on Rate (GFR): o As fibrosis progresses, GFR declines. o When the GFR drops below 60 mL/min/1.73 m², the clinical diagnosis of CKD is made. o End-stage renal disease (ESRD) occurs when GFR drops to less than 15 mL/min/1.73 m², and dialysis or kidney transplant becomes necessary. 3. Disease Transmission Transmission: o CKD is not a transmissible disease. It results from chronic disease processes (like diabetes, hypertension, and autoimmune disease) or gene:c muta:ons (as seen in polycysEc kidney disease). o There is no transmission from person to person unless there is a gene:c predisposi:on (e.g., in polycysEc kidney disease). 4. Risk Factors Risk factors for CKD can be classified into modifiable and non-modifiable risk factors. Modifiable Risk Factors Diabetes Mellitus: Poor blood glucose control can lead to diabe:c nephropathy, the leading cause of CKD. Hypertension: High blood pressure increases glomerular capillary pressure, leading to vascular sclerosis and nephron damage. Obesity: Increases metabolic demands on the kidneys, promotes insulin resistance, and raises blood pressure. Proteinuria: Increased protein in the urine is both a marker and a contributor to disease progression. Smoking: Induces vascular dysfuncEon and worsens CKD progression. Chronic Use of Nephrotoxic Drugs: Chronic use of NSAIDs (like ibuprofen) can damage renal tubular cells. Non-Modifiable Risk Factors Age: Aging increases suscepEbility to CKD due to glomerular sclerosis and loss of nephron units. Family History: GeneEc predisposiEons such as polycys:c kidney disease (PKD) increase risk. Ethnicity: African Americans, Hispanic Americans, and NaEve Americans have a higher prevalence of CKD. Gender: Males are more suscepEble to CKD progression than females, possibly due to hormonal influences. Summary Table  3 Criteria Chronic Kidney Disease (CKD) Most Likely Diabetes, Hypertension, GlomerulonephriEs, PKD, Autoimmune diseases. Cause 1. Nephron loss → 2. Hyperfiltra:on injury → 3. Tubulointers::al fibrosis Pathophysiology → 4. GFR decline. Not transmissible. CKD results from chronic disease, geneEcs, or toxic Transmission exposure. Modifiable: Diabetes, hypertension, obesity, smoking, NSAID use. Non- Risk Factors Modifiable: Age, family history, geneEcs (PKD), ethnicity, gender. Clinical Manifesta:ons Asymptoma:c Early Stages: CKD may go undetected unEl significant kidney funcEon is lost. Symptoms of CKD: o Uremia (build-up of urea in blood) leads to faEgue, nausea, and confusion. o Electrolyte Imbalances: Hyperkalemia (high potassium), metabolic acidosis, and fluid overload are common. o Anemia: Decreased producEon of erythropoie:n (a hormone produced by the kidneys) leads to reduced red blood cell producEon. o Cardiovascular Disease: PaEents with CKD are at high risk for cardiovascular complicaEons like le_ ventricular hypertrophy (LVH) and heart failure.