BIOL 218 Pathology Lecture Notes: Urinary System (Week 6, 2022) PDF

5) Excretory System (Urinary System Focus) A) Kidney Functions i. Endocrine Function (Review) a) Erythropoietin – produced in response to pO2 levels in kidneys target → red bone marrow → RBC synthesis (i.e. erythropoiesis)  O2 at high altitude stimulates erythropoietin release  RBC count (for...

5) Excretory System (Urinary System Focus) A) Kidney Functions i. Endocrine Function (Review) a) Erythropoietin – produced in response to pO2 levels in kidneys target → red bone marrow → RBC synthesis (i.e. erythropoiesis)  O2 at high altitude stimulates erythropoietin release  RBC count (for acclimation over days/wks) w/ side-effect being BP d/t polycythemia (i.e. increases blood viscosity) b) Renin (not rennin: enzyme produced in infant gastric glands to curdle milk) – produced in response to BP in renal arteries: Renin (JGA) Angiotensinogen Angiotensin I (inactive from liver) 10 a.a. ACE (lung/kidney endothelium) Angiotensin II (active enzyme) 452 a.a. 8 a.a. 1. Arteriolar smooth muscle constriction BP (i.e. direct vaso effect esp. on efferent arterioles) 2. ADH secretion  H2O reabsorption @ collect. ducts BP (hypo → post pit →) 3. Stimulates aldosterone production (by adrenal cortex)  Na+ reabsorption @ DCTs (active transport)  H2O reabsorption @ DCTs (osmosis = passive)  BP 47 ii) Metabolic Function a) Vitamin D activation (lack of produces rickets in kids = soft bones, a form of osteomalacia “bad bones”) 25-hydrocholecaliciferol (inactive) 1,25-dihydrocholecalciferol (active vitamin) (Note: refer to BIOL 228 Week 9 notes for multi-step activation process) - promotes Ca2+ absorption in gut via parathyroid hormone (PTH) b) Gluconeogenesis = glucose/new/making - glucose synthesis from non-glucose precursors (e.g. protein, fat) - primarily a liver mitochondria function, but kidneys help iii. Regulatory Function - maintains fluid and electrolyte balance (refer to Week 8 notes) Na+ (= Natrium) impt for H2O balance K+ (= Kalium) recall cardiac arrhythmias Ca 2+ Mg2+ hypo- vs normal range vs hyper- 48 iv. Excretory Function - elimination of metabolic wastes esp. nitrogen (N) from protein/DNA: - ammonia → urea from amino acid deamination in liver → N-waste - uric acid from nucleic acid breakdown → another N-waste in small amounts (if excess in blood then deposits in joints etc. causes gout) - creatinine from breakdown of creatine → muscle energy storage (from creatine phosphate: P transferred to ADP rapidly in one step compared to multi-step oxidative phosphorylation in cell respiration) - elimination of toxins (e.g. alcohol) or anything in excess → directly or after liver modification (e.g. alcohol dehydrogenase) Figure 24 FILTRATE BLOOD Longitudinal Section URINE 49 Nephron Anatomy (w/ blood supply simplified) Figure 25 INFLOW TAP OUTFLOW TAP Urine Formation (= Three Major Processes/Steps) a) Glomerular (Pressure) Filtration b) Tubular (Selective) Reabsorption c) Tubular Secretion (mostly, but some reabsorption: Na+, H+) 50 a) Glomerular Filtration (in "renal corpuscle") Figure 26 INFLOW TAP OUTFLOW TAP (= pores) What passes into filtrate? - water (180 L/day!) - small molecules: glucose, electrolytes, small hormones, wastes (e.g. ammonia, urea, uric acid, creatinine), meds (e.g. antibiotics) What remains in blood? - some water - RBCs, WBCs, platelets (i.e. all formed “cellular” elements) - plasma proteins (large molecules: albumins, globulins, fibrinogen) The forces behind filtration are a) GHP b) GCOP c) CHP influence GFR w/ GFR α GFP GHP = Glomerular Hydrostatic Pressure - the driving force behind filtration is the pumping of the heart (i.e. BP), specifically the LV 51 GCOP = Glomerular Colloid Osmotic Pressure – d/t osmotic backpull exerted on water by albumins (large plasma proteins from liver) CHP = Capsular Hydrostatic Pressure – backpressure (resistance) GFP = GHP – (CHP + GCOP) Figure 27 Glomerular Filtration Rate (GFR) is normally proportional to GFP (Glomerular Filtration Pressure): GFR α GFP i) ANS ii) Renin Regulation/Control of GFR inhibits iii) Autoregulation iv) ANH (ANP) 52 i) Autonomic Nervous System (ANS) The sympathetic portion of the ANS responds to: - shock - dehydration - hemorrhaging i.e. when blood volume drops, vasoconstriction of afferent arteriole shuts down blood flow to glomerulus  “inflow tap” turns off (i.e. arteriole lumen narrows) GFR and urine output (conserves H2O) Note: If GFP  then GFR approaches zero = acute kidney injury (AKI), which can result in chronic kidney disease (CKD) w/ permanent kidney damage if it persists. Nephron cells die b/c kidneys are not as resilient as liver cells! ii) Renin–Angiotensin–Aldosterone System (RAAS) If BP renin is secreted by juxtaglomerular cells in afferent arteriolar wall → angiotensin II is activated leading to vasoconstriction primarily in efferent arteriole  GFP (“outflow tap” turns off) (Also recall ADH and aldosterone) In addition, constriction of precapillary sphincters occurs in peritubular capillary network (so another outflow tap turns “off”) All result in GFP Maculae densa cells in walls of DCT adjacent to juxtaglomerular cells are sensitive to [ion] (which influences renin secretion) 53 iii) Autoregulation: intrinsic afferent arteriole dilation (inflow tap “on” i.e. arteriole lumen widens) and intrinsic efferent arteriole constriction (outflow tap “off”) can themselves increase GFR if BP drops iv) Atrial Natriuretic Hormone/Peptide (ANH/ANP) w/ Fx vs aldosterone If BP then heart produces ANH in response to right atrial stretching (preload) causing BP via inactivation of RAAS b) Tubular Reabsorption (by PCT) - Fx is to return impt materials to blood from filtrate using: i) Active Transport ii) Ionic Attraction (+/-) iii) Osmosis i) Active Transport e.g. glucose, amino acids, cations (e.g. Na+) desired materials (filtrate) active transport (at PCT) via peritubular capillary network into renal veins - specific protein carriers in cell membrane bind w/ each substance and ATP is used to transport them into cell (i.e. uniport)  amount of each that can be reclaimed is proportional to the number of available protein carriers, thus… renal threshold levels (maximums) exist e.g. In untreated diabetics, blood glucose is so high that glucose carriers are overwhelmed  excess glucose spills into urine. ii) Ionic Attraction – negatively-charged electrolytes (anions = Cl-, PO4-3, HCO3-) follow positively-charged electrolytes (cations) 54 Most electrolyte reclamation (= reabsorption) occurs in the PCT. iii) Osmosis – reclamation of all H2O is done osmotically w/ H2O following Na+ (b/c the kidneys can't actively transport water!) 70% of H2O is reclaimed in the renal cortex The rest (H2O) is reclaimed osmotically in the hypertonic (salty) renal medulla by the collecting ducts as H2O follows Na+: Figure 28 “countercurrent multiplier” Note: The purpose of Na+ pumps in the loop of Henle is to maintain a high [Na+] in the renal medulla. A hypertonic (salty) renal medulla allows the remaining H2O (i.e. ~ 30%) to be osmotically reclaimed. ADH (Vasopressin) controls water reclamation in the renal medulla: If ADH levels decrease then less H2O is reclaimed and it passes into urine (= diuresis). With certain drugs, med conditions, surgery and trauma, ADH levels increase  too much H2O is reabsorbed causing SIADH (= Syndrome of Inappropriate ADH secretion)  w/ risk of __. 55 c) Tubular Secretion (DCT specialty) Nephron cells can also pump materials out of blood: - small non-electrolyte molecules (e.g. penicillin and histamine) - H+ ions (w/ urine becoming more acidic to help control blood pH) - K+ ions w/ Na+ "in" (reabsorbed) and K+ "out" (secreted) = antiport (a Na+/K+-linked pump whose controlling hormone = aldosterone) Fluid remaining in the collecting ducts is no longer filtrate, but urine: ✓excess H2O ✓excess N-wastes/ions (salts) ✓other (incl. drugs) Voiding of Urine Urine collects in the renal pelvis and passes into the ureters w/ a valve b/w the ureters and urinary bladder to prevent backflow during micturition (= urination reflex). Urinary bladder – a muscular, elastic, extensible hollow organ lined w/ stretchy transitional epithelium: Figure 29 pyelonephritis→ upper UT cystitis → urinary bladder (attachment area) detrusor muscle (smooth i.e. involuntary) urethritis - exit past (voluntary) external and (involuntary) internal sphincters 56