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PHYSIOLOGY 2 ~ LECTURE 4 ~ SUNDAY ~ 3-7-2016 Increasing & decreasing GFR : we can`t tolerate increase & decrease in GFR “ in both cases BAD “ Increasing GFR → means variable substances such as [ H2SO4 bicarbonate , Glu , Amino acids are not completely reabsorbed , SO start to be in the urine “ THIS IS BAD “ Decreasing GFR → that`s mean waste product like urea & uric acid are accumulate in the body “ AGAIN .. THIS IS BAD “ IN BLEEDING : In bleeding you still need to remove the waste product from your body bleeding → result in decrease arterial blood pressure (BPa) → result in decrease renal blood flow (RBF)→ finally result in decrease GFR summary : Bleeding result in decrease Q , GFR , RBF because bleeding result in decrease GFR → might result in renal failure (RF) ; Everyone has bleeding we should stop it & you should bring the patient to normal cardiac output (Q) Renal failure ( RF ) : - RF may be : {we don`t know} 1- reversible damage 2- irreversible damage : it goes to chronic RF - Anyone have dehydration for any reason [ diarrhea , over sweating , vomiting , bleeding ] you should care about the kidney because it→ result in decrease GFR→ result in crystallization of tubule`s loop of henle →lead to permanent damage ,,, then you bring the blood to normal too late !! Distal tubules : early & late distal tubules between Afferent & Efferent arteriole (Aa & Ea) , it bunches the Aa & Ea Bleeding “normally “ decrease GFR→ result in decrease fluid reaching the distal tubules The cells where they touch the Aa & Ea called macula densa macula densa : sensory cells that sense how much Na+, K+ , Cl- reaching the distal tubules , so Macula densa part of distal tubules & sense for it , sense changes in sodium chloride level, and will trigger an auto regulatory response to increase or decrease Reabsorption of ions and water to the blood (as needed) in order to alter blood volume and return blood pressure to normal. Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016 a decrease in blood pressure results in less NaCl present at the distal tubule, where the macula densa is located. In bleeding ::: decreasing GFR , fluid , Na+ reaching distal tubules So we want to bring GFR to normal by increasing ,, the macula densa senses this drop in salt concentration and responds through two mechanisms : 1- one of them : First, it triggers dilation of the renal afferent arteriole, decreasing afferent arteriole resistance and, thus, offsetting the decrease in glomerular hydrostatic pressure caused by the drop in blood pressure. ,, Second, macula densa cells release prostaglandins, which triggers granular cells lining the afferent arterioles to release renin into the bloodstream. (The granular cells can also release renin independently of the macula densa),, They are also triggered by baroreceptors lining the arterioles, and release renin if a fall in blood pressure in the arterioles is detected. Furthermore, activation of the sympathetic nervous system stimulates renin release through activation of beta-1 receptors.) ,, Thus, a drop in blood pressure results in dilation of the afferent arterioles, increasing the GFR due to greater blood flow to the glomerulus - SUMMARY → macula densa cells Send impulses to Aa → result in dilatation of Aa [ you make more blood come to GC , more GFR ] 2- Another impulse - granule cells have granules → start secrete renin - renin-angiotensine system , causes constriction of the efferent arterioles, - decrease GFR due to bleeding , Increase renin production by granule cells lead to formation Angiotensine II (Angiotensinogene → Angiotensine I→ Angiotensine II) - Angiotensine II come back to circulation & make constriction in Ea not in Aa ; because Angiotensine II have receptor in Ea but don`t have in Aa , FINALLY that result in increase GFR SUMMARY : How kidneys protect itself : bleeding → decrease GFR → renin secretion → bring GFR to normal MEAN ARTERIAL BLOOD PRESSURE « « FIGURE 1 Systemic arterial blood pressure normally flocculated up & down ,, decrease in sleeping , urine exercise, digest , but GFR should not affect !! Mean BPa (Pm) increase between 70 -150 → GFR Is constant « This Is normal « - I take care of myself = auto regulation = from within Mean BPa (Pm) < 70 → GFR Is not constant (decrease) , the kidney Can not tolerate (no urine output ) ـــin normal case Pm does not decrease under 70 but in bleeding we want to decrease blood flow (in order to stop bleeding ) so pressure will decrease ـــ Mean BPa (Pm) > 150→ GFR Is not constant (increase) Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016 Figure 1 ( الشكل التالي مطلوب 70 150 mm Hg 140 70 150 contents of Urine: GENERAL NOTE : Substances filtrated through GC must have Mwt < 70K (70,000) g/mol Sample within bowman`s space contain plasma without protein ( the same as plasma ) GLUCOSE : GLU Mwt = 180 , so filtrated ; because less than 70k g/mol Plasma contain GLU 70-110 mg/ dl plasma “ not serum or blood “ If GLU in blood = 100 → you can take care & reabsorbed If GLU in blood =150 care less We have → Blood test to measure how much GLU in blood { depending on colors appear when touching with urine } No GLU in urine : CG = (GLU in urine / PG ) * urine output →( zero /100 )* 1ml/min = 0 ml/min GLU in GC freely filtered & completely reabsorbed , how ? Na-GLU carrier (carrier mediated transport ) « « Figure 2 Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016 الشكل التالي مطلوب Figure 3 proximal tubular cell HIGH LOW Blood Side Luminal side B l o o d s i d e =14 Eq/L =140 Eq/L In filtrate In filtrate Some times GLU may be appear in urine if GLU in plasma (high) >180 mg/dl - In feed status GLU does not exceed (150-160) , Sometimes not readily reabsorbed because it`s conc. In plasma high >180 mg/dl - if GLU > 180 GLU will appear in urine , this is called glycosuria → glucose in urine 12- carrier mediated transport : « « Figure 3 Facilitated diffusion ( carrier mediated transport ) : Saturation transport maximum (TMax) : protein carrier can transport limited amount of besieger → More conc. ~ More diffusion until reach TMAX , more conc. No more diffusion - Simple diffusion: 1- no saturation → no TMAX 2- More conc. ~ More diffusion (unlimited amount of besieger) Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016 Question : Analysis of the blood → the result indicated that : 1- GLU in blood = normal 2- GLU in urine = yes 3- hyperglycemia = no (GLU level in the blood ) ; because GLU level in blood = normal [ back to indicator no. (1) ] This result may be due to : 1- Inaccuracy of analysis 2- there is problem in the kidney → no. of carrier in the kidney less than normal called → nephrogenic glycosuria no Diabetogenic glycosuria FIGURE 4 الشكل التالي مطلوب T Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016 ~ SHORT NOTE : Gonorrhea ( ) السيالن: chronic inflammation ~ 1- dose must be taken along 1 week if patient take it for 2 days → formation of germs 2- Solving the problem : Big dose of “ for example “ amoxicillin it contain material combat removing by kidney through secretion SO , prevent amoxicillin from binding “ combat for the same receptor of amoxicillin “ that result in → not removed , not clean through urine for long time RED BLOOD CELLS No RBC in urine RBC >>>> protein ; because RBC contain membrane & billion of proteins in this membrane & hemoglobin If RBC present in urine→ may be from urethra , bladder , not glomerular Hematuria : blood in urine( ) البيلة الدموية Dr. considered that : painless hematuria is cancer unless complete investigation Types of Hematuria : a. macroscopic Hematuria → you can see it as a red color b. microscopic Hematuria → you can`t see it , but under microscope you can see RBC HEMOGLOBIN Mwt OF hemoglobin (HB) = 64000 g/mol so filtrated ; because less than 70k HB filtrated but we don`t see it in the urine ?! why ?! - because RBCs contain HB so it is not freely in the plasma ( HB inside RBC`s ) - half life of RBCs = 120 day , then HB leave RBCs to plasma (freely in plasma ) ,, but doesn`t filtrate ?! why ?! because freely HB bind to proteins & Mwt become more than 70k AMINO ACIDS Mwt of Amino acid = 110 g/mol , so filtered aminoaciduria ; because less than 70k Small amounts of amino acids are also present in normal urine Aminoaciduria : is the presence of amino acids in the urine.. Increased total urine amino acids may result from metabolic disorders, chronic liver disease or renal disorders. Aminoaciduria can be divided into primary and secondary aminoaciduria Amino acids : basic , acidic , and neutral→ have different carries Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016 Cystinuria : is an inherited autosomal recessive disease that is characterized by high concentrations of the amino acid cystine in the urine due to no carrier , leading to the formation of cystine stones in the kidneys, ureter, and bladder , It is a type of aminoaciduria.. Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016 FIGURE 5 الشكل التالي للفهم فقط Nermeen AL-Bkerat physiology (2) lecture 4 Sunday 3-7-2016