Ch 14 The Kidney - Learning Objectives

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PAS 517: Human Physiology & Pathophysiology I Chapter: 14: Kidney and Its Collecting System – Learning Objectives 1. Recall the different parts of the kidneys and state its function. 2. Tell the number of nephrons in each kidney and the blood flow it receives. 3. Distinguish between the functions of every nephron segment. 4. Differentiate between cortical and juxtamedullary nephrons. 5. Recognize the structures associated with kidneys and its significance. 6. List the functions of the kidney with relevant examples. 7. Explain the different steps in urine formation. 8. Apply the concept of urine formation to identify the substance that is mostly excreted versus the one that is mostly reabsorbed. 9. Describe the glomerular filtration process and identify the constituent of the filtrates. 10. State the normal GFR and recall its relationship with the perfusion pressure. 11. Dissect the different layers of the glomerular filtration barrier and identify its function. 12. Explain the determinants of GFR and its influence on urine formation. 13. Evaluate the effect of sympathetic nervous system, hormones and feedback controls on GFR. 14. Name the hormones affecting renal function and state the effect on GFR for a given hormone. 15. Define autoregulation and describe the process of Myogenic and Tubuloglomerular feedback. 16. Recognize the components of juxtaglomerular complex and state its function. 17. Apply the concept of Tubuloglomerular feedback and assess the outcome. 18. Calculate the renal clearance or GFR for a given substance using the formula and conclude if the substance is secreted or reabsorbed. 19. Recall tubular absorption is highly selective and match the biomolecules with their degree of reabsorption. 20. Describe transcellular, paracellular and osmosis transportation and sketch the transport of sodium, potassium, glucose, amino acids and hydrogen. 21. Explain the mechanism of formation of diluted versus concentrated urine. 22. Know the characteristics of normal urine. 23. Identify the clinical manifestations of specific renal diseases. 24. Differentiate between nephrotic and nephritic syndrome. 25. Judge if the given level of protein excretion falls under nephrotic or sub-nephrotic limits. 26. Point out the GFR in renal insufficiency and renal failure. Glomerular Diseases: 27. Recall the primary, secondary and hereditary glomerular diseases. 28. Describe the pathogenesis of glomerular injury, list the causes and identify the type of antibody causing the injury.
29. Outline the clinical categories of glomerular injury. 30. Describe the pathophysiology of nephrotic syndrome and recognize the clinical manifestation and complications. 31. State the causes of edema in nephrotic syndrome. 32. Interpret the given pathophysiological finding and match with specific disease. 33. Describe the microscopic and pathophysiological finding in minimal change disease, list the causes and the most common age group affected by the disease. 34. Describe the microscopic and pathophysiological finding in focal segmental glomerulosclerosis, list the causes and the most common age group affected by the disease. 35. Describe the microscopic and pathophysiological finding in membranous nephropathy, list the causes and the most common age group affected by the disease. 36. Recall the other causes of nephrotic syndrome. 37. Recognize the nephritic pattern and its targets. 38. Name some of the causes of nephritic syndrome. 39. Describe the microscopic and pathophysiological finding in post-streptococcal. glomerulonephritis, list the causes, clinical manifestations, diagnostic findings and the most common age group affected by the disease. 40. Describe the microscopic and pathophysiological finding in IgA nephropathy, list causes, clinical manifestations, diagnostic findings and the most common age group affected by the disease. 41. Name the lesions that occur in diabetic nephropathy and describe the glomerular and renal vascular lesions. 42. State the early manifestation of diabetic nephropathy and identify the albumin excretion range. 43. Outline the progression of diabetic nephropathy. Tubular and Interstitial Diseases 44. State the most common cause of acute kidney injury. 45. Discuss the causes, pathogenesis and clinical course of acute tubular injury. 46. Recognize the nephrotoxic injury by endogenous and exogenous agents and give examples. 47. Define pyelonephritis, discuss the etiology, most common route, disease course, risk factors, mechanism, clinical manifestations and prognosis of pyelonephritis. 48. List the reasons for why urinary tract infection is most common in females. 49. Differentiate between acute and chronic pyelonephritis. 50. Define chronic pyelonephritis, identify the causes and state the clinical features. 51. Discuss the stages, clinical course and prognosis of chronic kidney disease. Vascular Disease
52. Identify the important cause of secondary hypertension. 53. Discuss the pathogenesis and clinical course of renal artery stenosis. Cystic Diseases of the Kidney 54. Classify polycystic kidney disease (PKD) based on the inheritance pattern. 55. Compare and contrast autosomal dominant versus recessive PKD in terms of age of onset, gene mutation and clinical course. Urinary Tract Obstruction 56. Recall the four main types of calculi and name the most common one. 57. Explain the pathogenesis of stone formation and discuss the clinical course. Malignant Kidney Neoplasm 58. Name the most common malignant tumor of the kidney. 59. Discuss the risk factors, age group and the clinical course of renal cell carcinoma (RCC). 60. Recognize the clinical manifestations of RCC including the abnormal hormone produced and the site of metastasis.
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Diseases Background Pathogenesis Clinical features NEPHROTIC SYNDROME Podocyte dysfunction Causes: Massive proteinuria, Hypoalbuminemia, Edema, Hyperlipidemia, lipiduria Excessive glomerular permeability to plasma proteins. Edema: low serum albumin, inc renal sodium retention due to uncontrolled activation of epithelial sodium channel. Complications: infection and sepsis Thrombosis Acute kidney injury ESRD if heavy proteinuria not going into remission. Fatigue Frothy urine Anorexia Nausea & vomiting Abdominal pain Weight gain due to fluid retention Shortness of breath if having pleural effusion DVT, PE Minimal Change Disease IMP: does not need renal biopsy , >90% corticosteroids responsive can show defect, Selective proteinuria, no hypertension/ renal dysfunction in most pts. Most common in children , 90% less than 10-year-old Not visible in light microscope but in electron- it shows thinning (effacement) of the epithelial food processes (podocytes). Primary : idiopathic Secondary: drugs, neoplasm, infections and allergy Treatment: empirical Focal Segmental Glomerulosclerosis Most common nephrotic syndrome in adults Does not respond to corticosteroids (non-selective proteinuria) ON light microscope: Focal- only some glomeruli affected Segmental- only some part of the glomeruli affected Just like MNCD it causes effacement of food processes in all Primary: idiopathic Secondary: HIV, heroin abuse, healing of prior GN (igA, lupus), anabolic steroid abuse, inherited mutation Incidence of hematuria and HT higher Membranous Neuropathy Most common nephrotic syndrome in elderly. Slowly developing nephrotic syndrome Immune complex disease: IgG and C3 diffuse thickening of the glomerular wall throughout Primary: autoantibodies against podocyte antigens Secondary : Malignancy: solid tumors prostate, lung/GI, infection (Hepatitis C and B, syphilis), SLE, drugs High incidence of Deep vein and renal vein thrombosis and pulmonary embolism. GLOMERULAR DISEASE
Nephritic Syndrome Massive proteinuria, hyperlipidemia and hypoalbuminemia Nephritic pattern- glomerular inflammation--- inflammatory modulators attraction, cell proliferation—eventually causing permanent loss of function if not treated. Targets: Close to blood supply (mesangial, endothelium and GBM). Hypertension Oliguria Hematuria Peripheral edema Berger’s Disease (IgA neuropathy)- Most common cause of primary glomerulonephritis Post streptococcal Glomerulonephritis (PSGN) Caused by gram+ infection in the throat (streptococcus) Frank hematuria (after 1-4 weeks). Low C3 and normal C4 Complement system activation—immune complex deposition Hypocomplementemia and granular deposits of IgG and complement on GBM Children recovery faster and better than adults Hypertension Edema Azotemia Smoky brown urine Acute nephritic syndrome Some degree of proteinuria IgA nephropathy (Beggars disease) Caused by Upper renal infection Most common glomerular disease worldwide Children and young adults - gross hematuria 1-3 days after URI URI--- glycosylated IgA--- immune complex deposited in the mesangial --- alternative complement pathway activation---- glomerular injury. Gross hematuria after URI Its course is variable Most pts maintains normal renal function for a decade. 25-50%- SLOWLY PROGRESS TO END STAGE RENAL DISEASE over a period of 20 yrs.). Diabetic Neuropathy 2 nd only to MI as a cause of death from diabetes THREE LESIONS Glomerular Lesion - Capillary BM inflammation Diffuse Mesangial sclerosis Nodular glomerulosclerosis Renal vascular lesion - atherosclerosis and arteriosclerosis Pyelonephritis Microalbuminuria (>30 mg/day, <300mg/day)- macroalbuminuria, overt neuropathy, hypertension—END stage renal disease Tubular and Intestinal Disease Most common cause of acute kidney injury. (Acute renal Tubular Injury Persistent and severe disturbances in blood flow. Acute kidney injury- oliguria and dec GFR. Not all pts has oliguria: both anuric and
Acute Tubular injury/ Necrosis failure). Prognosis varies depending on the severity and nature of underlying disease. Caused by. Ischemia Nephrotoxic injury by endogenous (myoglobin Hb)/ exogenous (drugs, heavy metals, radiocontrast dyes ) non-oliguric forms are seen. Electrolyte abnormalities, acidosis, uremia and fluid overload . No treatment/ dialysis- death, w/ preexisting chronic disease- recovery less frequent and progression to end-stage renal diseases is common Pyelonephritis and UTI One of the most common kidney diseases. UTIs most common in women- shorter urethra, lack of antibacterial properties in prostatic fluid, hormonal changes affecting adherence of bacteria to mucosa, urethral trauma during sex (or combo) Inflammation affects the tubules, interstitium and renal pelvis. Mechanism: UT obstruction & urine statis, vesicoureteral reflux, intrarenal reflux. Caused by Gram negative E. coli bacteria present in GI tract (85%). Routes: Hematogenous infection Ascending infection- most common Colonization of the distal urethra and introitus--- multiplication of bacteria in bladder—it seeds to renal pelvis and papillae Risk factors: female sex, immunosuppression, indwelling catheters, diabetes mellitus & UT obstruction. Pain at costovertebral angle Systematic Evidence of infection- chills, fever, nausea, malaise UT signs- dysuria, frequency and urgency Urine appears turbid- pyuria (pulse in urine) Unilateral disease- do not develop renal failure Worst prognosis- papillary necrosis Chronic Pyelonephritis Chronic tubulointerstitial inflammation and scarring involve calyces and pelvis Imp cause of chronic disease Reflux neuropathy- most common cause. Superimposition of a UTI on congenital vesicoureteral reflux and intrarenal reflux. Chronic Obstructive Pyelonephritis: obstruction—kidney infection—scarring. Gradual onset of renal insufficiency Hypertension- asymmetrically contracted disease. Bilateral disease- hyposthenuria (dilute urine), manifested by polyuria and nocturia. Chronic Kidney Disease Final common pathway of progressive nephron loss from kidney disease Maladaptive nephron--- kidney scarring--- ESRD with sclerosed glomeruli, tubules, interstitium and vessels. Insidious onset Proteinuria, hypertension or azotemia Variable rate of prognosis
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Without treatment: death from uremia, electrolyte disturbance, or other complications ESRD . VASCULAR DISEASE Renal Artery Stenosis Can be cured and reversible Hypertension caused by inc production of renin from ischemic kidney. Common symptoms to essential HT Elevated plasma or renal vein renin IMP cause of secondary hypertension CYSTIC DISEASE OF THE KIDNEY AD polycystic kidney disease (Adult) Heredity- multiple expanding cysts of both kidneys—renal parenchyma destruction--- renal failure. Involves minority of nephrons initially (renal function intact till age 40-50) GENETIC PKD1 - cell- cell/ cell-matrix interaction (more severe) PKD2 - Ca 2+ permeable cation channel Cyst- abnormal extracellular matrix, cell proliferation and fluid secretion. Asymptomatic: hemorrhage or progressive dilation of cyst --- pain Kidney enlargement—dragging sensation Ft progressive chronic kidney disease like proteinuria (rarely more than 2gm per day) polyuria and hypertension . AR polycystic kidney disease (children) Perinatal, neonatal , infantile and juvenile. Hard to treat Mutation of PKHD1 gene - encodes fibrocystin (membrane protein w/ unknown function, Highly expressed gene in adult and fetal kidney and in liver, pancreas Pts may develop liver cirrhosis (congenital hepatic fibrosis) Older children—Hepatic disease is the concern--- portal hypertension w/ splenomegaly . URINARY TRACT OBSTRUCTION Urolithiasis (Renal Calculi, Stones) 4 types of calculi Calcium stones (70%) Triple stones/ struvite stones, composed of magnesium and phosphate. Uric acid stones Inc urinary conc of the stones constituents--- exceeds their solubility (supersaturation). Inc conc of stone constituents , changes in urinary pH, dec urinary volume and Prescence of bacteria influence formation of calculi, Asymptomatic or intense pain - suddenly occurs in the back and radiates downward and centrally toward the lower abdomen/ groin
Cysteine stones MALIGNANT KIDNEY NEOPLASMA Renal Cell Carcinoma Most common malignant tumor of kidney. 3% of all newly diagnosed cancers in US and 85% of renal cancers in adults. Most often in older ppl (>60 years) Sporadic/ heredity mutations---- chromosome 3p---- RCC Costovertebral pain, palpable mass and hematuria . Abnormal hormone production by tumor cells—polycythemia, hypercalcemia, hypertension, hepatic dysfunction, feminization/ masculinization, Cushing syndrome etc. Spreads widely (lungs, bones) before local symptoms/signs. GLOMERULAR DISEASES