Pathophysiology. Renal basic structure / function. Page 1. JP Advis DVM, Ph.D. Bartlett Hall, Animal Sciences, Cook, ,

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1 Pathophysiology JP Advis DVM, Ph.D. Bartlett Hall, Animal Sciences, Cook, , 17 Course website: rci.rutgers.edu/~advis Lectures, tests, grades, office hours, textbook, Material to be covered: About lecture slides: Lectures 1-2: Introduction to Pathophysiology (2) Lectures 3-4: Mechanisms of Self-Defense and Stress (2) Lectures 5-8: Endocrine and Nervous System Dysfunctions (4) Lecture 9: Alterations of Skeletal Muscle Function (1) REVIEW AND TEST #1 Lectures 12-18: Cardiovascular, Respiratory and Renal Dysfunctions (7) REVIEW AND TEST #2 Lectures 21-24: Alterations of Digestive Function and Intermediary Metabolism (4) Lectures 25-26: Alterations of the Reproductive System (2) REVIEW AND TEST #3 There are not intended to be the sole source for studying the course material!!!!!!!!!!!!!!!! Slides are good to review the course material after you have study your course textbook Slides are a good indicator of the relative importance of lecture topics (see slide # per topic Group slides by titles when using them to review course material. Match lectures and text. Renal basic structure / function infection The kidney s primary function is to maintain a stable internal environment for optimal cell and tissue metabolism. It also has an endocrine function, and also perform gluconeogenesis. The nephron, the functional unit of the kidney, has a glomerulus and a tubular component (PCT, HL, DCT) and empty its content into collecting ducts (CD), The JGA-MD has pressure and chemical receptors, is the area that produces renin, it is the target of renal inervation from the sympathetic ANS, and is involved in the autoregulation of GFR. About 20-25% of CO perfuse the kidneys every minute. A major hormonal regulator of RBF is the RAS. Aldosterone and ADH are the main endocrine regulators of blood volume and thus, BP. The counter-current mechanism, through NaCl secretion in the ascending loop of Henle, is the driving force for reabsorption of water from the collecting ducts. Overview of the structure / function of the kidney Page 1

2 Renal basic structure / function infection Urinary organs and kidney structure Adrenal gland Liver 12 th rib Right kidney Ureter Urinary bladder Spleen Renal artery Renal vein Left kidney Abdominal aorta Inferior vena cava Common iliac artery and vein Urethra Page 2

3 interlobular artery Capsule (fibrous) Renal column Renal sinus Hilium Renal pelvis Cortex Minor calices Major calices Renal papilla of pyramid Urether Medullary pyramids Medulla Renal basic structure / function infection The nephron and its tubular epithelial cells Page 3

4 PCT Glomerulus DCT HL (descending) CD HL (ascending) afferent arteriole viceral wall parietal wall JGA HL Papilla of pyramid DCT MD efferent arteriole Glomerulus PCT Bowman capsule Bowman space DCT Glomerulus Brush border PCT HL (thick) Intercalated cells Principal cells mitochondria HL (thin) CD (medullary) Page 4

5 Renal basic structure / function infection The nephron unit and its blood vessels Cortical nephron Efferent arteriole Afferent arteriole PCT Glomerulus DCT Juctamedullary nephron Interlobular artery and vein Arcuate artery and vein CD HL (descending) HL (ascending) HL Vasa recta Pyramid (medulla) Page 5

6 Renal basic structure / function infection Anatomy of the glomerulus and of the juxtaglomerular apparatus Efferent arteriole MD Glomerulus DCT JGA pores in endothelium Afferent arteriole parietal epithelia cell mesangial cell mesangial matrix viceral epithelium (podocytes) capillary lumen pseudofenestrations with central knob Bowman capsule basement membrane Parietal epithelial cell PCT Podocytes (viceral cell) podocyte cell body pedicel cell process capsular slits (filtration) capillary endothelium Page 6

7 Renal basic structure / function infection Structures of the urinary bladder Ureter Cut edge of peritoneum Smooth muscle Trigone Opening of ureter Opening of ureter Rugae Prostate gland External urinart sphincter Prostatic urethra Internal urinary sphincter Bulbouretheral gland Page 7

8 Renal basic structure / function infection Renal autoregulation RBF Flow rate (ml / min) GFR Arterial blood pressure (mm Hg) Page 8

9 Renal basic structure / function infection Cooperative roles of antidiuretic hormone and aldosterone in regulating urine and plasma volume sweating decreases H2O increases plasma volume / BP detected by JGA detected by renin release kidney Ag I ADH release posterior pituitary osmotic imbalance increases H2O reabs. Na Ag II lung adrenal gland K aldosterone release Page 9

10 Renal basic structure / function infection Major functions of nephron segments STRUCTURE glomerulus in Bowman s capsule PCT HL DCT CD FUNCTION filtration Reabsorption of: Na (majority) glucose K aminoacids HCO3 PO4 H2O Secretion of: H foreign Substances Concentration of urine Descending loop: H2O reabsorbed Na diffuses in Ascending loop: Na secretion H2O stays in Reabsorption of: Na H2O HCO3 Secretion of: K Urea H NH3 Some drugs Reabsorption of: H2O Reabsorption or secretion of: Na K H NH3 TONICITY OF FLUID WITHIN DUCTS isotonic Isotonis Hypertonic Hypotonic Isotonic or hypertonic Final concentration Page 10

11 Renal Dysfunctions infection is an interference with the flow of urine along the urinary tract. It might be anatomical or functional. Upper urinary tract s include compression of a calyx, ureteropelvic or ureterovesical junction (stones); compression from an aberrant vessel, tumor, or abdominal inflammation and scarring (retroperitoneal fibrosis); or ureteral blockage by stones or a malignancy of the renal pelvis, ureter, bladder, or prostate. Calculi or kidney stones are masses of crystals, proteins, or other substances that are a common cause or urinary tract. Lower urinary tract s are primarily related to storage of urine in bladder or emptying of urine through the bladder outlet. It might have a neurogenic and/or an anatomic origin (neurogenic bladder, overactive bladder syndrome, s to urine flow). Renal tumors, such as renal adenomas and renal cell carcinoma, and bladder tumors are often silent in onset and metastized to lung, lymph nodes, liver, bone, thyroid, and CNS. Examples of major renal dysfunctions Renal Dysfunctions: Obstructions infection Major sites of urinary tract Page 11

12 Ureteropelvic valve Hydronephrosis Polycystic kidney Ureteropelvic structure Fibrous band Dysplacia agenesis of ureter Stenosis Ureteral orifice Ureteral sphincter muscle in urogenital diaphragm Posterior vesicoureteral valve (reflux) Prostate hypertrophy Posterior vesicouretheral valve Uretheral stenosis Renal Dysfunctions: Obstructions infection Example of an upper urinary tract : Hydronephrosis with renal stones in pelvis & calyces Page 12

13 Renal stones Renal Dysfunctions: Obstructions infection Example of an lower urinary tract : Neurogenic detrusor overactivity with vesico-sphincter Page 13

14 Neurogenic Detrusor overactivity with Vesico- Spincter: narrowing of the sphincter (arrow) is consistent with EMG (line 6). See low urine flow (line 1) and volume (line 2), and high abdominal pressure (line 3). Pressure inside bladder (line 4) and in the detrusor muscle (line 5). 5 6 Renal Dysfunctions: Obstructions infection Example of an urinary tract due to a tumor: Renal cell carcinoma Page 14

15 Renal Dysfunctions: Infections infection infection (UTI) is an inflammation of the urinary epithelium usually caused by bacteria from gut flora. It can occur anywhere along the tract (urethra, prostate, bladder, ureter, kidney). Acute cystitis, is an inflammation of the bladder, the most common site of UTI. It may occur alone or in association with pyelonephritis or prostatitis. Painful bladder syndrome / intertitial cystitis (PBS/IC), is a condition that includes non-bacterial infectious cystitis (viral, mycobacterial, chlamydial, fungal), non-infectious cystitis (radiation, chemical, autoimmune, hypersensitivity), and intertitiak cystitis (of unknown origin, a persistent and chronic form of non-bacterial cystitis, with mast cell activation, altered epithelial permeability, and rise sensory nerve sensitivity). Acute pyelonephritis is an infection of renal pelvis and intertitium. Chronic pyelonephritis is a persistent or recurrent infection leading to scarring of the kidney. Examples of urinary tract infection (UTI) Page 15

16 Renal Dysfunctions: Infections infection Pyelonephritis, an urinary tract infection (UTI) of renal pelvis and interstitium Page 16

17 infection Glomerular disease might have a sudden or insidious origin. It is caused by an inflammatory process initiated by immune responses, metabolic disorders, or circulatory disturbances. It is the most common cause of chronic and end-stage renal failure. Glomerulonephritis is an inflammation of the glomerulus caused by immunologic abnormalities, ischemia, free radicals, drugs, toxins, vascular disorders, and systemic diseases including diabetes mellitus and lupus erythermatosus. Acute glomerulonephritis is often associated with streptococal or staphilococal infection. Sporadic occurrence have been observed after bacterial endocarditis, viral diseases (varicella, hepatitis B & C). Injury to glomeruli is immune mediated with Ag-Ab complex depositing on the glomerular basement membrane. It can evolve into a rapidly progressive glomerulonephrits (RPGN) and even to a chronic glomerulonephritis. Nephrotic syndrome is the excertion of >3.5 g of protein per day and is a characteristic of glomerular injury. Examples of glomerular disorders Glomerulonephritis infection Chronic glomerulonephritis Page 17

18 Renal Failures infection Acute renal failure (ARF) occurs over days or weeks, with low GFR, BUN, plasma creatinin and cystatin C levels. It might be associated with oliguria. There is an alteration in tubular function. They might be reversible if treated early. They are classified as: prerenal (low renal perfusion and GFR, ischemia and tubular necrosis); intrarenal (associated with several systemic diseases but commonly with acute tubular necrosis); and postrenal (associated with diseases that obstruct the flow of urine from the kidneys). Chronic renal failure (CRF) represents a progressive loss of renal function. Plasma creatinin levels gradually become elevated as GFR decreases; Na is lost in the urine; K is retained; acidosis develops; Ca and phosphate metabolism are altered and EPO production is disminished. All organ systems are affected by CRF. Examples of renal failures Page 18

19 Acute Renal Failure infection Mechanism of oliguria in acute renal failure Ischemia or nephrotoxins Possible glomerular injury Tubular injury (e.g. acute tubular necrosis) Intrarenal vasoconstriction Decreased permeability and decreased surface area Cellular cast formation Obstruction Tubular back leak Increased intraluminal pressure Decreased GFR OLIGURIA Page 19

20 Chronic Renal Failure infection Mechanism related to the progression of chronic renal failure Renal injury Loss of nephrons Increased Ag II Glomerular capillary hypertension Increased glomerular permeability and filtration Proteinuria Increased tubular protein reabsorption Systemic hypertension Tubulointertitial inflammation and fibrosis Renal scarring Page 20