Pathophysiology of Chronic Renal Failure
Introduction :-
Pathophysiology of Chronic Renal Failure- Renal failure refers to the failure of the kidney’s excretory function. It is usually characterized by a decrease in the glomerular filtration rate (GFR). As a result, GFR is thought to be the most accurate predictor of renal failure. However, the decrease in GFR is not as pronounced in the early stages of renal failure. Even if 50% of the nephrons are affected, the GFR decreases by only 20-30%. This is due to compensatory mechanisms in the unaffected nephrons. Renal failure can be either acute or chronic. There are always additional issues associated with renal failure, including:
1. Deficiency of calcitriol (active vitamin D) leads to decreased calcium absorption from the intestine and hypocalcemia. Calcitriol deficiency and hypocalcemia can lead to secondary hyperparathyroidism in some patients
2. Deficiency of erythropoietin causes anemia.
3. Disturbances in acid-base balance.
Chronic Renal Failure :-
Chronic Renal Failure- A condition known as chronic renal failure is marked by a gradual and permanent decline in renal function brought on by the gradual degradation of the renal parenchyma. If enough nephrons are destroyed, the illness can be fatal. Acidosis is the main problem in CKD with the development of biochemical azotemia and clinical uremic syndrome. When some nephrons lose function, unaffected nephrons can compensate. However, if more nephrons lose function over months or years, compensatory mechanisms fail and chronic renal failure develops.
Etiopathogenesis of Chronic Renal Failure :-
Chronic Renal Failure- All chronic nephropathies can lead to CRF. Diseases that cause CRF can generally be divided into two major groups: those that cause glomerular pathology and those that cause tubulointerstitial pathology. This classification is useful for facilitating research, but the disease is rarely limited to glomerular or tubulointerstitial tissue. In the end stage of CRF, all parts of the nephron are affected.
1. Diseases causing glomerular pathology Many glomerular diseases associated with CRF have an immune mechanism in their pathogenesis. Destruction of the glomeruli leads to alterations in the filtration process and the development of nephrotic syndrome, characterized by proteinuria, hypoalbuminemia and edema. The main examples of chronic glomerular diseases causing CRF are summarized under two headings: primary and systemic.
i) Primary glomerular pathology – The main cause of CRF is chronic glomerulonephritis, usually caused by various types of glomerulonephritis such as membranous glomerulonephritis, membranoproliferative glomerulonephritis, lipoid nephrosis (minimal change disease) and antiglomerular basement membrane nephritis.
ii) Systemic glomerular pathology: Certain diseases arise outside the renal system but cause secondary changes in the nephron. Important examples of this type are systemic lupus erythematosus, serum sickness nephritis, and diabetic
nephropathy.
2. Diseases causing tubulointerstitial lesions Damage to the tubulointerstitial tissue leads to alterations in reabsorption and/or secretion of vital components, resulting in excretion of large volumes of dilute urine. Tubulointerstitial diseases can be classified into four groups according to their causative etiology:
i) Vascular causes: Prolonged primary or essential hypertension causes characteristic changes in the renal arteries and arterioles, which are called nephrosclerosis. Nephrosclerosis causes progressive obstruction of renal vessels, eventually resulting in ischemia and necrosis of renal tissue.
ii) Infectious causes: A good example of a chronic kidney infection leading to CKD is chronic pyelonephritis. If this process progresses chronically, it leads to an increase in the number of nephrons and progressive damage, leading to CKD.
iii) Toxic Substances: Some toxic substances cause slow tubular damage, eventually leading to CKD. The most common example is taking large amounts of painkillers like phenacetin, aspirin, paracetamol etc (chronic analgesic nephritis). Other substances that may cause CKD after long term exposure include lead, cadmium and uranium.
iv) Obstructive Causes: Chronic obstruction of the urinary tract causes progressive damage to the nephrons due to fluid retention. Examples of this type of chronic damage include stones, blood clots, tumours, strictures and prostatic hyperplasia.
Stages of Chronic Renal Failure :-
Chronic Renal Failure is divided into five stages based on the glomerular filtration rate (GFR), which indicates how well the kidneys filter blood.
Stage 1: Kidney damage with normal or elevated GFR (more than 90 ml/min/1.73 m²). has no symptoms most of the time, although kidney damage can be structural.
Stage 2: Mildly reduced GFR (60-89 ml/min/1.73 m2). The patient may still be asymptomatic, but will have signs of kidney damage, including: Urine may include detectable amounts of protein B.
Stage 3: GFR declines moderately (30–59 ml/min/1.73 m²).Symptoms may include fatigue, anemia, and early bone disease.
Stage 4: GFR declines significantly (15–29 ml/min/1.73 m²).Symptoms become more severe and the patient is at higher risk for complications such as high blood pressure and cardiovascular disease. At this stage, approximately 90% of functioning kidney tissue is destroyed. GFR is approximately 10% of normal. The tubular cells have virtually no function. The result is loss of sodium and water regulation, leading to signs and symptoms of edema, metabolic acidosis, hypocalcemia, and uremia.
Stage 5: GFR or chronic renal failure or end-stage renal disease (ESRD).At this stage, the GFR is less than 5% of normal, resulting in a complex clinical picture of a uremic syndrome with progressive primary (renal) and secondary systemic (extrarenal) symptoms.
Causes of Chronic Renal Failure :-
Chronic Renal Failure has many causes and can permanently damage the kidneys. The most common causes are:
• Diabetes: High blood sugar levels can damage the small blood vessels in the kidneys and reduce their ability to filter waste products. One of the leading causes of chronic kidney disease (CKD) in the globe is diabetic nephropathy.
• High Blood Pressure (Hypertension): High blood pressure can damage the kidneys over time by putting additional strain on blood vessels, resulting in reduced kidney function.
• Glomerulonephritis: This is a group of diseases that cause inflammation of the filtering units or glomeruli of the kidneys, potentially causing chronic kidney damage.
• Polycystic Kidney Disease (PKD): A genetic disease characterized by the growth of many cysts in the kidneys, which over time cause the kidneys to enlarge and function less well.
• Obstructive Uropathy: Conditions such as kidney stones, tumors, and enlarged prostate can block the flow of urine and damage the kidneys over time.
• Chronic Pyelonephritis: Recurrent kidney infections can cause scarring and gradual loss of kidney function.
• Other Causes: Chronic use of certain medications (such as NSAIDs), autoimmune diseases (such as lupus), and environmental toxins can also cause chronic kidney failure.
Clinical Features of Chronic Renal Failure :-
Chronic Renal Failure- The clinical manifestations of full-blown CKD leading to the uremic syndrome are described in two Main headings: Primary (renal) uremic symptoms and Secondary (systemic or extrarenal) uremic symptoms:
A. Primary symptoms of primary uremic (renal) symptoms Uremia develops as the kidneys slowly fail. The resulting imbalance causes the following symptoms:
1. Acidosis metabolism Acid-base equilibrium is gradually lost as a result of renal failure. Excess hydrogen ions transpire as blood bicarbonate levels drop, resulting in metabolic acidosis. Clinical symptoms of metabolic acidosis include compensatory Kussmaul respiration, hyperkalemia, and hypercalcemia.
2. Hyperkalemia Because potassium is normally excreted primarily in urine, a decrease in GFR leads to excess accumulation of potassium in the blood. Hyperkalemia is exacerbated by metabolic acidosis. Clinical features of hyperkalemia are arrhythmias, weakness, nausea, intestinal colic, diarrhea, muscular irritability, and flaccid paralysis.
3. Sodium and Water Imbalance When GFR decreases, sodium and water cannot enter Bowman’s capsule adequately, resulting in Bowman’s capsule retention. Release of renin from the juxtaglomerular apparatus further exacerbates sodium and water retention. The main symptoms resulting from sodium and water retention are circulatory overload with hypervolemia and congestive heart failure.
4. Elevated blood sugar A reduction in GFR causes the blood to become too concentrated in uric acid. Uric acid crystals can accumulate in joints and soft tissues, causing gout.
5. Azotemia The waste products of protein metabolism are not excreted, leading to increased concentrations of urea, creatinine, phenol, and guanidine in the blood, causing biochemical abnormalities, azotemia. Secondary symptoms of uremia are related to the toxic effects of these metabolic waste products.
B. Symptoms of Secondary Uremic (Extrarenal) An abundance of extrarenal systemic symptoms arise as a result of abnormalities in fluid, electrolytes, and acid-base. Among them are:
1. Anemia Reduced erythropoiesis and anemia are caused by the sick kidneys’ diminished erythropoietin production. Moreover, anemia may be made worse by gastrointestinal bleeding.
2. The skin The skin appears pale yellow because of the pigments found in urine, such as urochromes. Sweat and blood plasma have higher urea contents. Urea is left on the face as a powdery substance known as “uremic frost” as perspiration evaporates.
3. Heart and Circulatory System Secondary effects of fluid retention include elevated cardiac workload from blood volume overflow and, in the end, congestive heart failure.
4. The respiratory system Pulmonary congestion and pulmonary edema are caused by backpressure resulting from blood volume overflow and cardiac failure. On a chest x-ray, uremic pneumonia is radiologically seen as having a central butterfly pattern of congestion and edema.
5. The digestive system’s azotemia directly causes mucosal ulcers in the stomach and intestines.
Further bleeding could make anemia already present worse. Diarrhea, vomiting, and nausea can all be brought on by gastrointestinal inflammation.
6. The Skeletal Structure Renal osteodystrophy is the term for renal failure’s skeletal symptoms.
Symptoms of Chronic Renal Failure :-
Chronic Renal Failure symptoms can develop gradually and may not become noticeable until considerable renal damage has taken place. Common indications and symptoms consist of There could be any of the following signs:
• Exhaustion and weakness;
• Swelling (edema) in the feet, ankles, or around the eyes;
• Changed patterns of urination (more, less, darker urine);
• Dyspnea, particularly in cases where there is fluid in the lungs;
• Persistent itching;
• Nausea and vomiting;
• Cramping in the legs;
• Appetite reduction and unintentional weight loss
• Lack of focus or perplexity
The following symptoms could appear when the condition worsens and causes complications: anemia, cardiovascular disease, bone disease, electrolyte imbalances, and anemia.
Conclusion :-
Chronic Renal Failure- In order to avoid problems and enhance quality of life, chronic kidney failure is a progressive, potentially fatal condition that needs to be identified early and treated effectively. Ongoing monitoring is also necessary. Patients can effectively treat chronic kidney failure and take proactive measures to safeguard their kidney health by being aware of the causes, symptoms, and available treatments. Patients with this chronic illness may get markedly better results with breakthroughs in medicine and a multidisciplinary approach.