Pathophysiology of Urinary System Disorders #8 PDF

Pathophysiology of Urinary System Disorders #8 Prepared By Prof. Zeinab Al-Wahsh HU Summer 2024  Urinary System  Removes metabolic wastes  Removes hormones from the body  Removes drugs other f...

Pathophysiology of Urinary System Disorders #8 Prepared By Prof. Zeinab Al-Wahsh HU Summer 2024  Urinary System  Removes metabolic wastes  Removes hormones from the body  Removes drugs other foreign material from body  Regulates water, electrolyte, acid-base balance  Secretes erythropoietin  Activates vitamin D  Regulate blood pressure through the renin- angiotensin-aldosterone system Copyright © 2019 by Elsevier Inc. All rights reserved. 2  The Glomerular filtration rate (GFR) is the most important index of renal function and is measured by the creatinine clearance test. The GFR is directly related to perfusion pressure in the glomerular capillaries.  The normal GFR is 125 ml/min in males and 115 ml/in women  The kidneys have an important endocrine function of producing erythropoietin (important for the production of red blood cells); and 1,25 –dihydroxy vitamin D3 ( important in the regulation of Ca++ metabolism). 7/12/2024 3  Renal blood flow is about 1000 to 1200 ml/min or 20 % 25% of cardiac output, so kidney is vulnerable to the toxic effects of drugs and chemicals  Normal protein excretion in the urine is less than 150 mg/day. Protein excreted in amounts greater than 150 mg/day is considered pathologic.  Factors that are important in preventing proteins from leaking through the glomerular filtration membrane during ultra filtration are the size of pores, it is too small to allow most proteins to pass; and both the glomerular filtration barrier and albumin molecules have a negative charge.  Persistent proteinuria is more likely to reflect some underlying renal or systemic disorders. 7/12/2024 4  Formation of Urine  Filtration In renal corpuscles Large volume of fluid passes from glomerular capillaries into the tubule (Bowman capsule). Wastes, nutrients, electrolytes, other dissolved substances Cells and protein remain in the blood.  Reabsorption Reabsorption of essential nutrients, water, and electrolytes into the peritubular capillaries Control of pH and electrolytes 5  Reabsorption  Transport mechanisms for reabsorption Active transport Co-transport Osmosis—water  Proximal convoluted tubules Most of water reabsorption Glucose reabsorption Nutrients and electrolytes to maintain homeostasis Copyright © 2019 by Elsevier Inc. All rights reserved. 6  Hormones Involved in Reabsorption  Antidiuretic hormone (ADH) Secreted by the posterior pituitary Reabsorption of water in distal convoluted tubules and collecting ducts  Aldosterone Secreted by adrenal cortex Sodium reabsorption in exchange for potassium or hydrogen Copyright © 2019 by Elsevier Inc. All rights reserved. 7  Incontinence and Retention  Incontinence Loss of voluntary control of the bladder  Enuresis Involuntary urination by child age older than 4 years Often related to developmental delay, sleep pattern, psychosocial aspect  Stress incontinence (more common in women) Increased intra-abdominal pressure forces urine through sphincter. Coughing, lifting, laughing Multiple pregnancies Copyright © 2019 by Elsevier Inc. All rights reserved. 8 Incontinence and Retention (Cont.)  Overflow incontinence Incompetent bladder sphincter Older adults Weakened detrusor muscle may prevent complete emptying of bladder—frequency and incontinence. Spinal cord injuries or brain damage Neurogenic bladder—may be spastic or flaccid Interference with CNS and ANS voluntary controls of the bladder Copyright © 2019 by Elsevier Inc. All rights reserved. 9 Incontinence and Retention (Cont.)  Retention Inability to empty bladder May be accompanied by overflow incontinence Spinal cord injury at sacral level blocks micturition reflex. May follow anesthesia (general or spinal) Copyright © 2019 by Elsevier Inc. All rights reserved. 10  Urinalysis: Appearance of Urine  Straw colored with mild odor Normal urine, specific gravity 1.010 to 1.050  Cloudy May indicate the presence of large amounts of protein, blood, bacteria, and pus  Dark color May indicate hematuria, excessive bilirubin, or highly concentrated urine  Unpleasant or unusual odor Infection or result from certain dietary components or medication Copyright © 2019 by Elsevier Inc. All rights reserved. 11  Urinalysis: Abnormal Constituents of Urine  Blood (hematuria) Small amounts Infection, inflammation, or tumors in urinary tract Large amounts Increased glomerular permeability or hemorrhage  Elevated protein level (proteinuria, albuminuria) Leakage of albumin or mixed plasma proteins into filtrate  Bacteria (bacteriuria) Infection in urinary tract Copyright © 2019 by Elsevier Inc. All rights reserved. 12  Urinalysis: Abnormal Constituents of Urine (Cont.)  Urinary casts Indicate inflammation of kidney tubules  Specific gravity Indicates ability of tubules to concentrate urine Low specific gravity—dilute urine (with normal hydration) High specific gravity—concentrated urine (with normal hydration) Related to renal failure  Glucose and ketones Found when diabetes mellitus is not well controlled Copyright © 2019 by Elsevier Inc. All rights reserved. 13  Blood Tests  Elevated serum urea and serum creatinine levels Indicate failure to excrete nitrogen wastes Caused by decreased GFR  Metabolic acidosis* Indicates decreased GFR Failure of tubules to control acid-base balance  Anemia* Indicates decreased erythropoietin secretion and/or bone marrow depression *In the absence of other problems. Copyright © 2019 by Elsevier Inc. All rights reserved. 14  Blood Tests (Cont.)  Electrolytes Depend on related fluid balance  Elevated renin levels Indicate kidney as a cause of hypertension Copyright © 2019 by Elsevier Inc. All rights reserved. 15  Other Tests  Culture and sensitivity studies on urine specimens Identification of causative organism of infection Help select appropriate drug treatment  Radiologic tests Radionuclide imaging, angiography, ultrasound, CT, MRI, intravenous pyelography Used to visualize structures and possible abnormalities, flow patterns, and filtration rates Copyright © 2019 by Elsevier Inc. All rights reserved. 16  Other Tests (Cont.)  Clearance tests Examples: creatinine or inulin clearance Used to assess GFR  Cystoscopy Visualizes lower urinary tract May be used to perform biopsy or remove kidney stones  Biopsy Used to acquire tissue specimens Copyright © 2019 by Elsevier Inc. All rights reserved. 17 Disorders of the Urinary System Urinary Tract Infections Cystitis and Urethritis Pyelonephritis Inflammatory Disorders Glomerulonephritis Nephrotic Syndrome Copyright © 2019 by Elsevier Inc. All rights reserved. 18  Urinary Tract Infections (UTIs)  Very common infections  Urine is an excellent growth medium.  Lower urinary tract infections Cystitis Urethritis  Upper urinary tract infections Pyelonephritis  Common causative organism Escherichia coli Copyright © 2019 by Elsevier Inc. All rights reserved. 19  Urinary Tract Infections (UTIs) (Cont.)  More common in women because of: Shortness of urethra Proximity to anus  Older men Prostatic hypertrophy Urine retention  Congenital abnormalities in children  Other common predisposing factors Incontinence Retention of urine Direct contamination with fecal material Copyright © 2019 by Elsevier Inc. All rights reserved. 20  Types of Urinary Tract Infections  Asymptomatic bacteriuria  Symptomatic infections  Lower UTIs Cystitis  Upper UTIs Pyelonephritis Causes of UTIs  The most common pathogens causing urinary tract infections are: E-coli (80%), and Klebsiella.  Lower urinary tract infections (UTIs) are more common in women because of their short urethra. In men, lower UTIs are usually associated with structural abnormalities and stasis resulting from obstructions. 7/12/2024 21  Cystitis and Urethritis  Bladder wall (cystitis) and urethra (urethritis) are inflamed. Hyperactive bladder and reduced capacity  Pain is common in pelvic area.  Dysuria, urgency, frequency, and nocturia  Systemic signs may be present. Fever, malaise, nausea, leukocytosis  Urine often cloudy, with unusual odor  Urinalysis indicates bacteriuria, pyuria, and microscopic hematuria. Copyright © 2019 by Elsevier Inc. All rights reserved. 22  Pyelonephritis  One or both kidneys involved  From ureter into kidney  Purulent exudate fills pelvis and calyces.  Recurrent or chronic infection can lead to scar tissue formation. Loss of tubule function Obstruction and collection of filtrate → hydronephrosis Eventual chronic renal failure if untreated Copyright © 2019 by Elsevier Inc. All rights reserved. 23  Pyelonephritis (Cont.)  Signs of cystitis plus pain associated with renal disease Dull, aching pain in lower back or flank area  Systemic signs include high temperature.  Urinalysis Similar to cystitis Urinary casts are present. Reflection of renal tubule involvement Copyright © 2019 by Elsevier Inc. All rights reserved. 24  Inflammatory Disorders: Glomerulonephritis  Many forms  Presence of antistreptococcal (ASO) antibodies Formation of an antigen-antibody complex Activates complement system Inflammatory response in glomeruli Increased capillary permeability—leakage of some protein and large numbers of erythrocytes  Severe inflammatory response Congestion and cell proliferation Decreased GFR—retention of fluid and wastes Copyright © 2019 by Elsevier Inc. All rights reserved. 25  Nephrotic Syndrome  Abnormality in glomerular capillaries, increased permeability, large amounts of plasma proteins escape into filtrate  May be idiopathic in children 2 to 6 years old  May be secondary to SLE, exposure to nephrotoxins or drugs 26  Pathophysiology Hypoalbuminemia with decreased plasma osmotic pressure Subsequent generalized edema Blood pressure remains low or normal. May be elevated depending on angiotensin II levels Increased aldosterone secretion in response to reduced blood volume More severe edema High blood cholesterol, lipoprotein in urine, lipiduria with milky appearance to the urine 27  Signs and Symptoms  Proteinuria, lipiduria, cast  Massive edema  Sudden increase in girth 28 Urinary Tract Obstructions Urolithiasis Hydronephrosis Tumors 29  Urolithiasis (Calculi)  Can develop anywhere in urinary tract  Stones may be small or very large.  Tend to form with: Excessive amounts of solutes in filtrate Insufficient fluid intake—major factor for calculi formation Urinary tract infection  Manifestations only occur with obstruction of urine flow. May lead to infection Hydronephrosis with dilation of calyces If located in kidney or ureter and atrophy of renal tissue 30  Urolithiasis (Calculi) (Cont.)  Calculi composed of calcium salts High urine calcium levels Form readily with highly alkaline urine  Uric acid stones Hyperuricemia Gout, high-purine diets, cancer chemotherapy Especially with acidic urine  cystine stones  Stone formation depends on predisposing factor. 31  Signs and Symptoms  Stones in kidney or bladder often asymptomatic Frequent infections may lead to investigation. Flank pain possible caused by distention of renal capsule  Renal colic caused by obstruction of the ureter Intense spasms of pain in flank area Radiating into groin area Lasts until stone passes or is removed Possible nausea and vomiting, cool moist skin, rapid pulse Radiologic examination confirms location of calculi. 32  Tumors Renal Cell Carcinoma Bladder Cancer Copyright © 2019 by Elsevier Inc. All rights reserved. 33  Renal Cell Carcinoma  Manifestations Painless hematuria initially Gross or microscopic Dull, aching flank pain Palpable mass Unexplained weight loss Anemia or erythrocytosis Paraneoplastic syndromes Hypercalcemia or Cushing syndrome 34  Bladder Cancer  Most bladder tumors are malignant and commonly arise from transitional epithelium of the bladder.  Often develops as multiple tumors  Diagnosed by urine cytology and biopsy  Early signs Hematuria, dysuria Infection common  Tumor is invasive through wall to adjacent structures. Metastasizes to pelvic lymph nodes, liver, and bone 35  Bladder Cancer (Cont.)  Predisposing factors Working with chemicals in laboratories and industry Particularly aniline dyes, rubber, aluminum Cigarette smoking Recurrent infections Heavy intake of analgesics  Treatment Surgical resection of tumor Chemotherapy and radiation Photoradiation successful in some early cases 36  Renal Failure Copyright © 2019 by Elsevier Inc. All rights reserved. 37  Acute Renal Failure  Causes Acute bilateral kidney diseases Severe, prolonged circulatory shock or heart failure Nephrotoxins Drugs, chemicals, or toxins Mechanical obstruction (occasionally) Calculi, blood clots, tumors Block urine flow beyond kidneys 38  Acute Renal Failure (Cont.)  Sudden onset  Blood tests Elevated serum urea nitrogen and creatinine levels Metabolic acidosis and hyperkalemia  Treatment Identify and remove or treat primary problem. To minimize risk of necrosis and permanent kidney damage Dialysis To normalize body fluids and maintain homeostasis 39 7/12/2024 40 Causes of Renal Failure: Nephrotoxins Copyright © 2019 by Elsevier Inc. All rights reserved. 41 Causes of Renal Failure: Ischemia Copyright © 2019 by Elsevier Inc. All rights reserved. 42 Causes of Renal Failure: Pyelonephritis Copyright © 2019 by Elsevier Inc. All rights reserved. 43  Chronic Renal Failure  Gradual irreversible destruction of the kidneys over a long period of time  Asymptomatic in early stages  May result from Chronic kidney disease Congenital polycystic kidney disease Systemic disorders Low-level exposure to nephrotoxins over sustained period of time 44  Chromic Renal Failure Causes 7/12/2024 45  Chronic Renal Failure: Stages  Decreased renal reserve Decrease in GFR Higher than normal serum creatinine levels No apparent clinical symptoms  Renal insufficiency Decreased GFR to about 20% of normal Significant retention of nitrogen wastes Excretion of large volumes of dilute urine Decreased erythropoiesis Elevated blood pressure Copyright © 2019 by Elsevier Inc. All rights reserved. 46  Chronic Renal Failure: Stages (Cont.)  End-stage renal failure Negligible GFR Fluid, electrolytes, and wastes retained in body Azotemia, anemia, and acidosis (three As) All body systems affected Marked oliguria or anuria Regular dialysis or kidney transplantation To maintain patient’s life Copyright © 2019 by Elsevier Inc. All rights reserved. 47  Chronic Renal Failure  Early signs Increased urinary output General signs Anorexia Nausea Anemia Fatigue Unintended weight loss Exercise intolerance Bone marrow depression and impaired cell function Caused by increased wastes and altered blood chemistry Elevated blood pressure Copyright © 2019 by Elsevier Inc. All rights reserved. 48  Chronic Renal Failure (Cont.)  Complete failure Oliguria Dry, pruritic, hyperpigmented skin, easy bruising Peripheral neuropathy Impotence in men, menstrual irregularities in women Encephalopathy Congestive heart failure, dysrhythmias Failure to activate vitamin D Possible uremic frost on the skin Systemic infections Copyright © 2019 by Elsevier Inc. All rights reserved. 49  Diagnostic Tests  Metabolic acidosis becomes decompensated.  Azotemia  Anemia becomes severe.  Serum electrolyte levels may vary depending on the amount of water retained in the body. Usually hyponatremia and hyperkalemia occur, as well as hypocalcemia and hyperphosphatemia. Copyright © 2019 by Elsevier Inc. All rights reserved. 50  Treatment  All body systems are affected.  Difficult to maintain homeostasis of fluids, electrolytes, and acid-base balance  Drugs to stimulate erythropoiesis  Drugs to treat cardiovascular problems  Intake of fluid, electrolytes, protein must be restricted  Dialysis or transplantation Copyright © 2019 by Elsevier Inc. All rights reserved. 51 Factors Determining the Manifestations of Renal Failure The extent of renal function that is present Coexisting disease conditions The type of renal replacement therapy that the person is receiving Disorders of Water, Electrolyte, and Acid-Base Balance  Sodium and water balance The kidneys function in the regulation of extra cellular fluid volume  Potassium balance Approximately 90% of potassium excretion is through the kidneys In end stage of renal failure systemic acidosis causes K+ to shift from the cells to the extra cellular fluid. 7/12/2024 52  Acid-Base balance The kidneys normally regulate blood pH by eliminating hydrogen ions produced in metabolic processes and regenerating bicarbonate. A person with end-stage renal failure is probably in metabolic acidosis ❖ Hematologic Disorders Accompanying Renal Failure Anemia Coagulopathies ❖ Cardiovascular Disorders Accompanying Renal Failure Hypertension Heart disease Pericarditis 7/12/2024 53  Acid-Base balance The kidneys normally regulate blood pH by eliminating hydrogen ions produced in metabolic processes and regenerating bicarbonate. A person with end-stage renal failure is probably in metabolic acidosis ❖ Hematologic Disorders Accompanying Renal Failure Anemia Coagulopathies ❖ Cardiovascular Disorders Accompanying Renal Failure Hypertension Heart disease Pericarditis 7/12/2024 54  Uremic patients may have attacks of gouty arthritis because urate salts are deposited in the joints and soft tissues.  The probable cause of pruritus (itching) in chronic renal failure is Ca++ deposits in the skin  Common pulmonary complications in end- stage renal failure are pneumonitis and pulmonary edema  Internal metabolism of proteins , carbohydrates and fats are all abnormal in ESRD.  Increased parathyroid hormone secretion results in increased renal reabsorption of calcium  7/12/2024 55  Hypertension is linked with kidney, because renal diseases my be both the cause and consequence of increased blood pressure.  Hypertension is common in ESRD and may be result of the release of rennin secondary to abnormal handling of salt and water. The hypertension produces cardiac hypertension and congestive heart failure.  Azotemia is indicated by a sharp rise in the serum creatinine and BUN above normal values and generally signals of ERRD. 7/12/2024 56  Metabolic acidosis in uremia occurs because the failing kidneys are no longer able to excrete the daily acid load resulting from fewer functioning intact nephrons.  Manifestations of gastrointestinal involvement in the uremic syndrome are vomiting; diarrhea; anorexia.  There is a blunting of the immune response in most patients with ESRD, characterized by impairment of the acute inflammatory response, leukocyte count may b normal , but the leukocyte function is abnormal resulting in increased risk of infection.  Infection may be difficult to detect because uremic patients tend to have less fever in response to infection. The cause of uremic hypothermia is believed to be a result of inhibition of to Na-K pump. 7/12/2024 57  Hyperkalemia develops in ESRD because of renal excretory failure. A rise in serum K+ to 7 or 8 mEQ/L may result in fatal cardiac dysrhythmia.  A normocytic , normochromic anemia typically occurs in ESRD resulting from decreased production of erythropoietin.  Disturbances in blood coagulation, occur as a result of impaired platelet aggregation in ESRD.  The typical mouth odor in uremic syndrome is due to ammonia produced from urea-splitting bacteria in the mouth. 7/12/2024 58 7/12/2024 59