kidney physiology

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kidney (Q & A)

Q. List different Functions of the kidney (A) Homeostatic function;

1. Regulation of water and electrolyte balance. 2. Regulation of acid-base balance. 3. Regulation of arterial blood pressure. (B) Excretory function;

1. Excretion of metabolic waste products e.g. urea, uric acid, creatinine. 2. Excretion of foreign chemicals e.g. drugs and food additives. 3. Excretion of excess Na+, K+, H+ or HCO 3 -. (C) Endocrinal function;

1. 2. 3. 4.

Kidney secretes:

Erythropoietin; 85% (stimulate production of RBCs). 1,25 dihydroxy cholecalciferol (Active vitamin D3 )  Ca homeostasis. Renin (activate angiotensinogen into ang I  ang II which increase ABP). Prostaglandins (PGI2 which is vasodilator, Thromboxane A2 which is vasoconstrictor).

kidney (Q & A)

Q. Describe the Functional anatomy of the kidney ►The renal mass is divided into 2 major regions. a.  An outer Cortex: granular and darker in colour. b.  An Inner medulla: striated and paler in colour. The kidney is composed of 6 - 18 lobes. Each lobe consists of a pyramid of medulla covered with cortex. - The medulla is divided into renal pyramids. - Each pyramid taper to form a renal papilla. - Each papilla projects into the pelvic space via minor calyx. - The minor calices converge into 2 or 3 major calices, which Converge to form the pelvis of the ureter.

Q. Describe the functional characteristics of nephron  Nephron is the functional unit of the kidney, composed of: a) Renal corpuscle It is formed of Glomerulus (Tuft of capillaries) which lies within the dilated blind end of renal tubule (Bowman’s capsule). capsule). These capillaries lies between afferent arteriole and a smaller efferent arteriole ►Glomerulus is a high pressure capillary bed  (60 mmHg) .

b) Renal tubule

The total length of renal tubule is 45-65mm 1) Proximal convoluted tubule (PCT  ) - lies in the cortex . - It coils and twists in the neighborhood of its renal corpuscle. - It is made up of single layer of cells. 2) Loop of Henle medulla. - U shaped that dips in the renal medulla. - It is composed of: a) Thin segment i.e. descending limb and lower ½ of  ascending limb. It is lined by flat epithelium. b) Thick segment i.e. rest of ascending limb (lined by cuboid epithelium and contain many mitochondria. 3) Distal convoluted tubule DCT  - 5 mm long that lies in the cortex . - It opens into the cortical collecting tubule. 4) Collecting ducts medulla . - 20 mm that passes through cortex and medulla.

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Q. Describe the location and structure of the juxtaglomerular apparatus  Area of contact between the distal convoluted tubule and the afferent arteriole of the same nephron. Present in cortical nephrons only.

@ It consists of; (1) Macula densa ; (intra-renal chemoreceptors) modified tubular cells in 1st part of DCT secrete a substance directed towards arteriole. Macula densa cells detect changes in volume of Na delivered to the distal tubules. - Macula densa in the juxtaglomerular apparatus → release of vasoactive chemicals (in case of  increase in blood pressure) → afferent arteriolar vasoconstriction → decrease in RBF & GFR or  vasodilator substance leading to afferent arteriolar vasodilatation (in case of decrease in blood pressure) → increase in RBF & GFR. (tubuloglomeular feedback). (2) Juxta glomerular cells; (intra-renal baroreceptors) Granular cells Modified smooth muscle fibres in the wall of afferent arteriole Secrete renin. (3) Lacis cells: found in the interstitium between the juxtaglomerular cells and macula densa, Their function is unknown. @ Function; - Auto-regulation of renal blood flow and glomerular filtration during changes in ABP. - Regulation of blood pressure and sodium balance.

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kidney (Q & A)

Q. Distinguish between a renal corpuscle and a renal tubule.  A renal corpuscle is a tangled cluster of blood capillaries called a glomerulus. The glomerulus surrounds a glomerular capsule that marks the enlarged, closed end of arenal arenal tubule. tubule. The renal tubule contains the fluids secreted by the blood in the renal corpuscle.

Q. Compare between Types of nephrons  

Items

% Of total Glomeruli Loop of Hnle

Cortical nephrons 85 % Out part of cortex Short i.e. dips to the junction between inner and outer medulla. It has no thin ascending limb. The thin descending limb joins the thick ascending limb at the hairpin loop. Peritubular capillaries No Vasa Recta Na reabsorption Thick muscular wall Very sensitive to symp Stimulation. Have JG apparatus Exhibit autoregulation autoregulation Low resistance to blood flow at rest Thin muscular wall Less sensitive to symp Stimulation & vasopressin.

Juxtamedullary nephrons

15% Inner part of cortex Long i.e. dips deeply into the medullary pyramids to the inner  medulla. The ascending limb is formed of a thin part and a thick part. Blood supply Vasa recta and peritubular  capillaries Special function Urine concentration Afferent arteriole Thin muscular wall Less sensitive to symp Stimulation. Have no JG apparatus Do not exhibit autoreg High resistance to blood flow at rest Efferent arteriole Thick muscular wall Very sensitive to symp Stimulation & vasopressin. Tone decreased by Prostaglandins (PGs). JG apparatus Present Absent Autoregulation Present Absent The efferent vessels of juxtamedullary glomeruli form long looped vessels, called Vasa recta which is important for urine concentration.

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kidney (Q & A)

Q. Describe Blood supply of the kidney k idney Kidneys receive 20-25% of cardiac output i.e. 1.2-1.3 litre / min.(1200ml/min). min.(1200ml/min). 90% to the cortex, 9% in outer medulla & 1% in inner medulla. Renal vascular arrangement: Each renal artery divides to form the interlobar arteries, arcuate arteries (100mmHg ) and interlobular  arteries  afferent arterioles  glomerular capillaries (60mmHg) efferent arterioles peritubular capillaries (13 mmHg) (also vasa recta)  interlobular veins  arcuate veins (5-8mmHg)  interlobar veins  renal veins.

The most unique feature of the renal microcirculation is the presence of two capillary  beds in series;

Glomerular  capillary bed

Peritubular  capillary bed

1. Receives bl from afferent art. 2. High presure bed 60 mmHg 3.Represents arterial end of cap. 4. allows fluid filtration.

Receives bl from efferent art. Low pressure bed 13 mmHg Represents venous end of cap.  Allows fluid reabsorption & specialized for O2  supply.

►Portal

system (capillary beds in series), paralleling the nephron

Renal ==> afferent ==> glomerular ==> efferent  ==> peritubular  arteries ==> arterioles ==> capillaries ==> arteriole s ==> capillaries.

Q. Name the vessels the blood passes through as it travels from the renal artery to the renal vein. The route the blood follows is: renal artery to several interlobar arteries, to arcuate arteries, to afferent arterioles, to efferent arterioles, to peritubular capillaries, to interlobular veins, to arcuate veins, to interlobar veins, to a renal vein.

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Q. List Characteristics of renal circulation 1- Very rich, rich, high flow circulation (25% of cardiac output). 2- It is a portal circulation i.e. blood flows through 2 sets of capillaries (the glomerular and peritubular  capillaries) before it drained by veins. The renal circulation is the only circulation where there are capillaries which are drained by arterioles (glomerular capillaries drain in efferent arterioles). 3- High permeability of permeability of glomerular capillaries. 4- High pressure in glomerular capillaries (glomerular capillary pressure is 50-60 mmHg, in other  parts of the body is average 25mmHg) facilitates filtration of plasma. 5- Pressure in peritubular in peritubular capillaries is relatively low which low which favors reabsorption of solutes and fluids from renal tubular lumen to capillaries. 6- High degree of autoregulation of autoregulation..

Q. what is the effect effect of Sympathetic Sympathetic on the kidney - Vasoconstriction of afferent & efferent arterioles via  receptors. - Renin secretion from juxtaglomerular apparatus. - Increased Na+ reabsorption of renal tubules.

Q. Discuss how renal blood flow is regulated Kidneys receive 20-25% of cardiac output i.e. 1.2-1.3 litre/min. litre/min. So renal plasma flow (RPF) about 625 ml/min. ml/min. 90% to the cortex, 9% in outer medulla & 1% in inner medulla. urine Low medullary blood flow is due to high resistance offered by vasa recta and is important for  for urine concentration. concentration.

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kidney (Q & A)

 A) Autoregulation of the renal blood flow  @ DEF; RBF is kept relatively constant between ABP; 80-180 mmHg, It is present in denervated, isolated kidney, This proving that this property is intrinsic property . - Beyond blood pressure range 80 – 180 mmHg, there is no autoregulation.

@ mechanism; by changing the renal vascular resistance. a. Myogenic mechanism - Increased ABP  stretch of afferent arteriole  increased Ca influx from extracellular fluid into muscle fibre  direct vasoconstriction  prevent increase in RBF. - Smooth muscles in the wall of afferent arteriole relax when blood pressure decreases leading to vasodilatation causing increase in blood flow and increase in GFR back to normal. b. Tubuloglomerular feedback - Macula densa in the juxtaglomerular apparatus → release of vasoactive chemicals (in case of  increase in blood pressure) → afferent arteriolar vasoconstriction →decrease in RBF & GFR or  vasodilator substance leading to afferent arteriolar vasodilatation (in case of decrease in blood pressure) → increase in RBF & GFR. Distal tubule

Efferent arteriole

Bowman’s capsule

Proximal tubule

Macula densa

Afferent arteriole

Glomerulus

GFR increases.

Flow through tubule increases.

Flow past macula densa increases.

Granular cells

2

Paracrine diffuses fr om macula densa to afferent arteriole. Afferent arteriole constricts.

Resistance in afferent arteriole increases. Collecting duct Loop of Henle

Hydrostatic Hydrostatic pressure in glomerulus decreases. GFR decreases.

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kidney (Q & A)

2- Extrinsic  Extrinsic regulation:  A- Hormonal regulation:  - adrenaline and noradrenaline cause constriction of renal vessels leading to a decrease in RBF. - angiotensin II in high levels constrict both afferents and efferents leading to a decrease in RBF. - prostaglandins may be vasodilators or vasoconstrictors. B- Extrinsic sympathetic nervous control: constricts renal vessels leading to decrease in RBF and decrease in glomerular filtration rate (GFR).

Q. Explain how the PTC is adapted for reabsorption. Because the efferent arteriole is narrower than the peritubular capillary, the pressure of the blood in the capillary is relatively low. Also, the walls of the capillary are more permeable than those of other  capillaries. These factors enhance the rate of fluid reabsorption.

Q. Describe how to measure renal blood flow By PAH clearance ►The substance used is PAH (paraminohippuric acid) because - If is freely filtered by the glomerulus. - It is completely secreted from the peritubular capillaries into the tubular lumen in single circulation.

►Measurement of the effective renal plasma flow ERPF. The extraction ratio of PAH is 90% 90 % i.e. only 90% of PAH in renal arterial blood is removed in a single circulation. This is because only 90% of ARPF go to the nephrons   Actual RPF = ERPF.x 100/90. ►Measurement of the actual (total) renal blood flow RBF Knowing the haematocrite value. RBF = RPF / 1 – HV = about 1200 mL/min

Q. List different processes needed for Formation Of Urine 1) Glomerular filtration: filtration : into Bowman’s capsule. 2) Tubular reabsorption: reabsorption : from lumen to peritubular capillaries. capillaries. 3) Tubular secretion: secretion : from peritubular capillaries to lumen.

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Q. What are the characters of glomerular filtration a- Contents: Contents: - water  - ions: Na+, K+, Cl- freely filtered substances e.g. glucose, amino acids. - 0.03% albumin (molecular weight 6900). b- Osmolality : 300 mosmol/L, isotonic (same osmolality as plasma). C- Specific gravity : 1010 D- pH : drops to 6 in urine due to acidification by the kidney. Glomerular filtration rate (GFR) In an average man: man: 125 ml/minute. ml/minute. In women : 10% less. Tends to decrease with advanced age (60% less at 70 years). High renal blood flow (20-25% of cardiac output) needed for high GFR. GFR equals about 180 about  180 L/day so L/day so plasma volume (3L) filtered about 60 times daily, this important to excrete large amount of waste products. More than 99% of GFR is normally reabsorbed.    



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kidney (Q & A)

Q. Define Filtration fraction It is the fraction of the renal plasma flow (RPF) that becomes glomerular filtrate. the average filtration fraction about 16-20%. It is calculated as (GFR/RPF X100).

Q. Describe the structure of Glomerular capillary membrane (1) Capillary endothelium; It has small holes (70-90 nm). It does not act as a barrier against plasma protein filtration. (2) Basement membrane; (BM) filamentous layer attached to glomerular endothelium & podocytes, carry strong-ve charges which prevent the filtration of plasma proteins, but filters large amount of H2 O and solutes. (3) Podocytes; Epithelial cells that line the outer surface of the glomeruli. They have numerous foot processes that attach to the BM, forming filtration slits s lits (25 nm wide).

There are stellate cells called mesangial cells between basal lamina and endothelium. They are contractile cells and and play a role in glomerular filtration.

Q. Describe Permeability characters of the glomerular membrane Size of the molecules

Substances having diameters less than 4 millmicrons (molecular weight 5500) are freely filtered while those having diameters more than 8 millimicrons (molecular weight more than 7000) are not filtered. Charges of the molecules

-ve charged molecules are filtered Less easily than neutral molecules of equal size. (possibly  due to negative charges in the basement membrane).

Q. List different Forces (dynamics, mechanism) that control GFR Forces favoring Filtration: 2 Hydrostatic pressure in glomerular capillary = 60 mmHg. Colloidal smotic pressure of proteins in the filtrate = 0 mmHg . Forces opposing Filtration: 2 Hydrostatic pressure in Bowman’s capsule = 18 mmHg  Colloidal osmotic pressure of proteins in glomerular capill= capill= 32 mmHg  The net filtering pressure 60 - 50 = 10 mmHg.

kidney (Q & A)

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Q. Define Filtration coefficient (Kf) It is the GFR / mmHg of net filtration pressure, it is normally 12.5ml/min/mmHg. It is constant (normally). * Glomerular filtration rate =Net filtration pressure X Filtration coefficient GFR = NFP (l0) X K f  (12.5) = 125ml/min. - K f f  is determined by 2 factors: 1- The permeability of the capillary bed. 2- The surface area of the capillary bed. K f  = permeability of membrane X effective filtration surface area (of both kidneys).

Q. Compare the composition of glomerular filtrate with that of the blood plasma. The glomerular filtrate has about the same composition as what becomes tissue fluid elsewhere in the body. In other words, glomerular filtrate is mostly water and contains essentially the same substances as blood plasma, except for the larger protein molecules.

Q. Mention different Factors that affect GFR (1) Changes in glomerular  in  glomerular hydrostatic hydrostatic pressure.  pressure. (I) Diameter of the afferent arterioles. a. VD of afferent arterioles Increased Hydrostatic pressure in glomerular capillary  Increase GFR. b. VC of afferent arterioles e.g Increased sympathetic activity  Decreased Hydrostatic pressure in glomerular  capillary  Decreased GFR. (II) Diameter of the efferent arterioles; arterioles ; 1. Moderate VC  increase glomerular capillary hydrostatic pressure  Slight increase of GFR. 2. Severe VC  decrease RBF  decrease GFR. (III)  ABP; Between 70 & 170 mmHg: GFR and RBF are kept relatively relativ ely constant by autoregulatory mechanisms. mechanisms. (IV) RBF : direct relation with GFR. (V) Sympathetic stimulation: only with severe sympathetic stimulation, afferent arterioles constricted leading to decreased GFR. (2) Changes in Bowman’s Capsule hydrostatic pressure hydrostatic  pressure Increased Hydrostatic pressure in Bowman’s capsule e.g. stone in ureter  Decrease GFR. (3) Change in glomerular  in  glomerular colloidal colloidal osmotic pressure osmotic pressure Increased Colloidal osmotic pressure in glomerular capillary e.g in dehydration decreased GFR. Decreased Colloidal osmotic pressure in glomerular capillary e.g in hypoproteinemia  increased GFR. (4) Renal vasodilators - Prostaglandins synthesis in kidneys is increased by haemorrhage haemorrhage (due to sympathetic stimulation and Increased angiotensin II). This may protect the renal vessels from severe VC. (5) Functioning kidney  Functioning  kidney mass: When the number of functioning nephrons decreases e.g. in renal disease (failure), there is reduction of filtration coefficient (kf) & decrease in GFR (decreasing the filtering surface area).

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(6) Changes in filtering  in  filtering surface surface area: This is changed by contraction or relaxation of mesangial cells. They are contracted by vasopressin (ADH), adrenaline, angiotensin II, prostaglandin F2 and sympathetic stimulation. They are relaxed by prostaglandin E2 , dopamine, cAMP and ANP. Contraction of mesangial cells → decrease surface area available for filtration → decrease in Kf  & decrease in GFR and vice versa. (7) Changes in the permeability the  permeability of  glomerular membrane  glomerular  membrane: GFR is directly proportional to the permeability of glomerular membrane e.g. hypoxia, fevers, some renal diseases increases this permeability.

Q. How GFR is evaluated A) Clearance tests: (1) Inulin clearance; Inulin has the following following characteristics:  Freely filtered i.e. plasma conc.= filtrate concentration.  not reabsorbed or secreted by renal tubules i.e. amount filtered per min.= amount excreted in urine/min.  Not metabolized.  Not stored in the kidney.  Does not affect filtration rate & its conc. is easily measured. (2) Creatinine clearance  Freely filtered  Not reabsorbed  partially secreted by renal tubules.  Endogenous so used easily but inaccurate.

B) Blood tests: Blood levels of urea of  urea and creatinine elevated in severe decrease in GFR.

Q. Discuss Renal Plasma Clearance ► Definition

It is the volume of plasma that is completely cleared of the substance excreted in urine per minute. ►Calculation

 Amount cleared from plasma/min= amount excreted in urine /min. C X P = U X V C= volume of plasma cleared from substance/min. P= conc. of the substance per 1 ml plasma. C = U X V  U= conc. of the substance per 1 ml urine P  V= volume of urine per minute. ► Importance

of the determination of plasma clearance

Study of tubular  of  tubular handling  handling of  of different  different solute solute in the filtrate the  filtrate Reabsorbed (glucose, urea, H 2 O.), Secreted (creatinine, PAH). 1-Inulin:

Freely filtered in glomeruli, not reabsorbed and not secreted. secreted. All the amount given is completely filtered and completely excreted in urine i.e. the amount of  plasma filtered / minute is completely cleared from inulin. So, C IN  IN  = GFR = 125 ml. / min.

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kidney (Q & A)

2-Urea clearance:

Urea is freely filtered, partially reabsorbed and no secretion. So, urea clearance is less than GFR (the amount of urea excreted in urine is less than that filtered). Curea = 70 ml / min. 3-Glucose:

It is freely filtered and completely reabsorbed and no secretion. i.e. all filtered glucose returns back to plasma and no glucose is excreted. C glucose = Zero / min. 4-Para-aminohippuric acid (PAH) clearance: (Exogenous).

It is freely filterable, almost complete secretion in one single circulation (90%) with no absorption. So, it is used for measurement of RBF. Why? a- It is not metabolized and not stored nor produced by the kidney. b- It does no affect RBF. c- Its level can be measured easily. d- 90% is removed from the blood in a single circulation. CPAH = Effective RPF (625 ml/ min.) -The actual renal plasma flow = 700 ml / min. (90% only filtered in single circulation). By knowing the hematocrit value, RBF can be calculated = 1270 -Diodrast is Diodrast is also handled in the same manner as PAHA so can be used to measure effective renal   plasma flow (ERPF). 5- Creatinine clearance:

- Mode of handling: complete filtration, partial secretion, no reabsorption. So,creatinine So,creatinine clearance is more than GFR = 140 ml/min. - It is an endogenous substance coming from creatine metabolism in skeletal muscles. It is released into blood at relatively constant rate. - It can be used clinically for measuring GFR, it is easier but it is inaccurate. Substance Inulin Urea Glucose PAH Creatinine

 

Tubular handling Neither reabsorbed or secreted Partially reabsorbed Completely reabsorbed Completely secreted Partially secreted

Clearance(mL/min) 125 Less than 125 0 625 125-625

Free water clearance: (CH2O ): Free water clearance (C  H20  H20 ): C H20 = V - C osm U osm x V

=VP osm

C H20 is + ve when urine is hypotonic and - ve when urine is hypertonic. i.e. in hypotonic urine more free water than solute is excreted and in hypertonic urine less water than solute is excreted.  Alteration in water metabolism produced by ADH Osmotic load excreted is 700 mosm/day.

Q. define the renal plasma clearance , and explain why the clearance of inulin is equal to the glomerular filtration rate.

kidney (Q & A)

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Q. List different functions of renal tubules 1- Reabsorption: Transport of substance from lumen of tubule to blood. 2- Secretion: addition of substance to the glomerular glomerular filtrate coming from from blood . 3- Synthesis: addition of new substance to glomerular filtrate e.g ammonia.

Q. Describe how substances transported along the renal tubules Types of transport across the tubular epithelium 1) Transcellular : through cells. 2) Paracellular : through the tight junctions between the cells. Mechanism of tubular transport A) Active transport; against electrochemical gradient. (1) Primary active transport Requires energy directly from ATP.  ATPase is a component of a carrier (transporter). ►Primary active transporter include - Na+ - K+ ATPase for Na+ reabsorption in PCT. (2) Secondary active transport - It does not require energy directly from ATP. a) Co-transport  Two substances bind to a specific carrier are cotransported in one direction. e.g. secondary active transport of glucose. b) Counter-transport  Two substances bind to a specific carrier are transported in two directions e.g. secondary active secretion of Hydrogen. B) Passive transport: Down electrochemical gradient. i. Simple diffusion: Transport of substance is down electrochemical gradient e.g. lipid soluble substances. ii.Facilitated diffusion: Transport of substance is down electrochemical gradient and requires a carrier e.g. non- lipid soluble substances.

Q. List different Characteristic features of PCT

- PCT is about 15 mm long and 55 μm in diameter. - PCT wall is lined by single layer of epithelial cells that are connected by tight junctions at their luminal edges, but there is a space between the cells along the rest of their lateral borders (lateral intercellular  spaces) which contains interstitial fluid. - The luminal borders of cells have brush border due to presence of large number of microvilli which increase surface area for reabsorption. - The PCT cells have large numbers of mitochondria (energy supply).

Q. Discuss how tubular reabsorption is a selective process. Tubular reabsorption causes the composition of the filtrate to change before it is excreted as urine. For  instance, glucose is present in the filtrate, but is absent in the urine. Urea and uric acid are considerably more concentrated in the urine than they are in the glomerular filtrate. This is accomplished through the epithelium of the renal tubule.

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kidney (Q & A)

Q. Discuss functions of PCT (1) Reabsorption o o

o o o

o

o

65 % of filtered Na+ (active), Cl- and water are reabsorbed (passive). The rate of PCT reabsorption of Na+ and water depends directly on GFR. This is called glomerulotubular balance. balance. + 80 % of filtered K is actively reabsorbed.  About 80 to 90 % of HCO 3 - is reabsorbed actively. Reabsorption of 60 % of filtered Ca+2 and 80 % of filtered phosphate. ( parathyroid  parathyroid hormone inhibits phosphate reabsorption). reabsorption).  About 50% of the filtered urea is reabsorbed passively because walls are partially permeable to urea. This is called back diffusion of urea. urea. Glucose, amino acids and trace of proteins are completely reabsorbed by active processes. (secondary active). active).

Na reabsorption 65% is reabsorbed by primary active transport. ► At the basolateral border of tubular epithelium Na+ - K+ ATPase pump Extrude 3 Na+ ions into the interstitium in exchange with 2 K+ ions that are pumped into the cell. This decreases intracellular Na+ concentration and creates -ve potential. ► At the luminal border  + Na diffuses from the lumen to the cell passively.

kidney (Q & A)

Glucose reabsorption - Complete reabsorption Site & Mechanism - Site; early portion of the proximal convoluted tubules. - Secondary active reabsorption i.e cotransport with Na. Na: The glucose and Na bind - Cotransport with Na: to a common carrier (called SGLT2) (sodiumdependent glucose transporter). As Na moves down its electrochemical electrochemical gradient, glucose is carried into the cells. - This transport is Na + dependent. - Glucose is transported from cell to interstitial fluid by facilitated diffusion utilizing a carrier  called GLUT2 (glucose transporter). Renal threshold for glucose plasma level at which glucose first appears in urine (180 mg/dl). Tubular maximum for glucose (TmG) The maximum amount of glucose (in mg ) that can be reabsorbed per min. It equals the sum of TmG of all nephrons. TmG not the same in all nephrons It is an indication of the reabsorptive capacity of the kidney. It is determined by the number of glucose carriers in PCT. The maximum reabsorption rate is reached when all the carriers are fully saturated so they can not handle any additional amounts at that time. Value; 300 mg/min in ♀ , 375 mg/ min in ♂. Glucosuria Excretion of glucose in urine in considerable amounts. It leads to osmotic diuresis with loss of Na + and K+. ►Causes; 1. Diabetes mellitus: blood glucose level > renal threshold. 2. Renal glucosuria: glucosuria: It is caused by the defect in the glucose transport mechanism. 3. Phlorhizin:  A plant glucoside which competes with glucose for the carrier  and results in glucosuria (phloridzin diabetes). 4. Pregnancy : due to altered glucose handling in distal nephrons.

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Phosphate reabsorption Phosphate is reabsorbed mainly in i n PCT (80%),Secondary (80%), Secondary active transport with Na. PTH inhibit PO 4 reabsorption.

Bicarbonate Handling Plasma HCO3 - plays an important role in the regulation of pH of plasma.

Amino acids and protein reabsorption - Amino-acids are transported by secondary active transport using the same carrier of Na (there are many carriers ,one specific for acidic, other for basic and another for neutral amino acids). - Proteins are transported in the PCT by the process of pinocytosis.(active) pinocytosis.(active) - Proteins in the filtrate about (5mg%).

H2O reabsorption - 65 - 67% of filtered load reabsorbed, Following Na by osmosis. - Sodium absorption → passive water absorption in the proximal tubule (Obligatory reabsorption), this is because: because: a- The walls of the proximal tubule are highly permeable to water. b- As the solutes are reabsorbed, an osmotic gradient for water is created and water follows the solute. - Since, almost equal amounts of Na & H2 O (65 - 67%) of each reabsorbed in proximal CT. The iso-osmotic with tubular fuid and Na+ conc. The fluid at the end of proximal tubule absorbed fluid is iso-osmotic with → iso-osmotic .

(2) Secretion in the Proximal Convoluted Tubule a- Substances from the blood : e.g. PAH, creatinine (active secretion), drugs. b- Substances formed inside PCT cells : e.g H+ (active), ammonia (passive).  Secretion of H + in PCT  This is formed in the tubular cell from dissociation of H2 CO 3 to H+& HCO 3 - then is secreted at the luminal border of the cells by 2 ry  active transport  in exchange with Na+ reabsorption utilizing an antiport carrier .  Synthesis & secretion of ammonia in PCT  The PCT cells synthesize ammonia (NH3 ) from glutamine. NH3 & H+ are secreted, combine at the luminal border to form ammonium ion (NH4 +) which excreted in urine urine in the the form of ammonium chloride, sulfate or phosphate.

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Q. Describe the permeability characters of Loop Of Henle The LH constitutes a counter-current system (a system in which the inflow runs parallel, in the opposite direction and close to the outflow). The LH of the cortical nephrons (conservation of Na+ & water ). ). The LH of juxtamedullary nephrons (urine concentration). concentration). The main function of LH  is to create an osmotic gradient in the renal medullary interstitium (in  juxta-medullary nephrons).

Descending thin segment O . - Highly permeable to H2 O and reabsorbed 15-20% of filtered H 2 2 O  - This is obligatory reabsorption i.e. not controlled by hormones. - The fluid reaching the tip of the loop is hypertonic and reaches equilibrium with medullary interstitium 1200-1400 mosm. mosm.

Thin ascending limb of LH Small amount NaCl reabsorbed passively into the medullary interstitium.

Thick ascending limb - 25% - 30% of Na+ reabsorbed. - K+ and CL are cotransported at luminal border dependin g on Na+- K+ pump at basolateral border. fluid becomes hypotonic 100 mosm. - This part is impermeable to water and urea. So the tubular fluid + + - The -  The 1 Na , 1 K and 2 Cl co-transporter in the luminal membrane act using the energy released by diffusion of sodium down an electrochemical gradient into the cells. There is a slight backleak of  potassium ions into the lumen, creating a positive charge (about +8 millivolts) in the tubular lumen.

- The positive charge (+8 mV) of the tubular lumen relative to the interstitial fluid forces, so cations such as Mg+2 and Ca+2 diffuse from the lumen to the interstitial fluid via the paracellular pathway.

Therefore, tubular fluid is iso-osmotic at beginning of loop, hypertonic at tip of loop and hypotonic at end of loop,  falling to a concentration of about 100 mOsm/L as it flows toward the distal tubule.

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kidney (Q & A)

Q. Explain how hypotonic tubular fluid is produced in the ascending limb of the nephron loop The ascending limb of the nephron loop is impermeable to water but diffuses electrolytes by transport mechanisms. This causes its fluid to be hypotonic with respect to the interstitial fluid surrounding it.

Q. Explain why fluid in the descending limb of the nephron is hypertonic Because the descending limb of the nephron loop is very permeable to water yet almost impermeable to solutes, its fluid is hypertonic with respect to the interstitial fluid surrounding it.

Q. Discuss function of Distal convoluted tubule & cortical Collecting duct Reabsorption   Active reabsorption of Na ; followed by passive chloride & bicarbonate reabsorption, in exchange with H or K secretion, under the control of  aldosterone. aldosterone.

+

 Water reabsorption - Only 5% of filtered water is absorbed by DCT & about 15 % in CD. - The water permeability in DT is low, so little water is absorbed. - ADH increases the permeability of DT & CD to water, so water passes passively down the osmotic gradient in the hypertonic medullary interstitium. In absence of ADH (Diabetes Insipidus), the permeability permeability of CD is very low & large volume of urine is excreted that may exceed 20 L/day with osmolality  down to 100 mosmol./L.  Reabsorption of water in DT & CD is called Facultative water  reabsorption but in the proximal tubules is called  Obligatory water reabsorption (65 %).

kidney (Q & A)

20

 Chloride reabsorption

Passive (down electric gradient) and by secondary active transport with Na.  Reabsorption of Ca By primary active transport (increased by parathyroid hormone).

Secretion  Synthesis of NH 3 increases in cases of acidosis. It combines with H + and forms ammonium salts.  H + Secretion H+ is secreted by 1 ry active transport.  Potassium (K + ) secretion It is actively secreted in DT & CD. K+ secretion is coupled to Na + reabsorption, reabsorption, K + secretion is regulated by aldosterone by  aldosterone hormone. hormone .

Q. List The functional characteristics of the late DT and cortical CD 1. They are almost completely impermeable to urea. 2. They reabsorb sodium ions and Cl - follows passively. 3. They actively secrete potassium ions. 4. The intercalated cells of these nephron segments secrete hydrogen ions by primary active transport. Both hydrogen and potassium compete for secretion. The rate of sodium reabsorption and active secretion of potassium and hydrogen is controlled by aldosterone. by  aldosterone. 5. The permeability of the late distal tubule and cortical collecting duct to water is controlled by the concentration of ADH.

kidney (Q & A)

21

Q. What is the function the inner medullaryCD.

1) Urea reabsorption  ++ osmolarity of medullary interstitium, which is essential in renal ability to excrete concentrated urine. 2) H 2 2 O reabsorption  ADH causes opening of H 2 O channeles.

Q. List The major Hormones that affect the renal tubules of the kidney 1-  Antidiuretic hormone It increases the water permeability of the collecting ducts of the kidney 2-  Aldosterone It stimulates sodium reabsorption in exchange with K or H  by  by the late distal tubules and collecting ducts. 3- Parathyroid hormone It increases distal renal tubular calcium reabsorption. It reduces the proximal tubular reabsorption of phosphate. The final composition of urine determined at the level of distal nephron (DCT & CD).

22

kidney (Q & A)

Water Handling It is a passive process throughout throughout the whole nephron.

(1) Obligatory H 2 O reab

(2) Facultative H 2 O reab

87% of filtered H2 O About 13% of filtered H2 O Independent of ADH Controlled by ADH Secondary to solute reabsorption by osmosis, Independent of solute reabsorption so, it so no change intraubular fluid osmolality. changes urine concentration (osmolality) 1. PCT 65% 2. loop of Henle 15% 1. Cortical collecting tubule 3. DCT 5% 2. Medullary duct 4. Collecting duct 25%  PCT contains aquaporin (water channels) in the luminal membrane.

Q. Describe Regulation of tubular reabsorption (1) Glomerulo tubular balance  ++ reabsorption of solutes and, in turn, H2 O. ►Site; PCT (main site) and loop of Henle. ►It is prominent for Na, the renal tubules reabsorb a constant percentage of the filtered Na rather than a constant amount. ►mechanism: ++ GFR  ++ colloidal osmotic pressure in the peritubular capillaries  ++ reabsorption of  solutes and, in turn, H2 O. ►Definition; ++ GFR

(2) Transtubular Physical factors . Reabsorption by the peritubular capillaries  favour  reabsorption 1-  Forces that  favour reabsorption a) The colloidal osmotic pressure of peritubular capill= capill = 32 mmHg. b) The hydrostatic pressure in renal interstitium = 6 mmHg. 2-  Force that oppose that  oppose reabsorption c) The hydrostatic pressure inside peritubular capill.= 13 mmHg. d) The colloidal osmotic pressure of renal interstilium= interstilium = 15 mmHg Net reabsorptive Net reabsorptive force  force = (32 + 6) – (13 + 15) = 10 mmHg.

(3) Hormonal control; A) Mineralocorticoids e.g Aldosterone. They act on DCT to increase i ncrease Na reabsorption in + + exchange with K or H . B) Angiotensin B) Angiotensin II : most powerful Na+ retaining hormone by direct action of PCT and via aldosterone. C) Glucocorticoids; have weak mineralocorticoid activity D) ADH; increase H2O reabsorption in DCT and CD. (ANP): inhibiting Na+ reabsorption in distal tubules. E) Atrial natriuretic peptide (ANP):

(4) ABP; decrease Na+ excretion via - Inhibition of rennin angiotensin system → ↓ renin and angiotensin II production. - ↑ Hydrostatic pressure in peritubular capillaries which → increase Na+ & H2 O excretion.

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23

Q. Define Glomerulotubular Balance & explain its explanation -The ability of the tubules to increase reabsorption rate in response to increased tubular load (increased tubular inflow) - Ensures that the reabsorption rate of the proximal tubule is matched to the glomerular filtration rate. - Helps to prevent overloading of distal tubular segments when GFR increases - Refers to the fact that the total rate of reabsorption increases as the filtered load increases, even though the percentage of GFR reabsorbed in the proximal tubule remains relatively constant at about 65 per cent - It is independent of any hormones

- Two mechanisms: (1) Oncotic and hydrostatic pressures between the peritubular capillaries and the lateral intercellular space (i.e. Starling’s forces) This protein-rich plasma leaves the glomerular capillaries, flows through the efferent arteriole, and enters the peritubular capillaries. The increased oncotic pressure in the peritubular capillaries augments the movement of solute and fluid from the lateral intercellular space into the peritubular capillaries. This action increases net solute and water reabsorption by the proximal tubule. (2) increase in the filtered load of glucose and amino acids - As GFR and the filtered load of glucose and amino acids increase, Na+ and water reabsorption also rise.

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Q. Describe how the kidney concentrate Urine Renal mechanisms for excreting concentrated urine: (1) High ADH level (2) Hyper-osmotic gradient of renal medulla.

Mechanisms that produce hyperosmotic gradient include: (1) (2) (3) (4)

The counter current multiplier system. The counter current exchanger system of the vasa recta. Diffusion of large amount of urea from the medullary collecting ducts into medullary interstitium. Sluggish medullary flow 1 - 2 % of RBF, this minimizes solute loss from the medullary interstitium.

Counter Current Multiplier  Descending  limb ►Descending limb Very permeable to H 2 O. Much less permeable to NaCL and urea. Therefore, the tubular osmolarity gradually rises from 300 to 1200 mOsm/L at the tip of the loop due to: a. Osmosis of H2 O out of the descending limb. b. Diffusion of NaCL from the medullary interstitium into the descending limb.

 

 Result ;

The interstitium fluid makes osmotic equilibration with the descending limb being H2 O permeable. Thus the interstitial fluid forms a hyperosmotic gradient starting from300 from300 mOsm/L at superficial layers of medulla and reaches 1200 mOsm/L at deep layers of the medulla.

 Ascending  limb ► Ascending limb a) Thick segment It is absolutely impermeable to H2 O, but Na +, K+ and Cl- are cotransported  Actively into  Actively into the renal medulla. b) Thin segment NaCL is passively  is passively reabsorbed reabsorbed into the medullary interstitium Result; The tubular fluid becomes hypotonic 100 mosm as it enters the distal tubule.

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kidney (Q & A)

Counter Current exchanger ►

In the descending limb descending  limb

(Vasa recta)

of the vasa recta

a)Solutes a) Solutes diffuse from the medullary interstitium to the blood along concentration gradient. b)Water b) Water diffuses from the blood to the medullary interstitium. ► Result: ►

At the tip of vasa recta, blood osmolality = 1200 mOsm/L.

In the ascending limb ascending  limb

of the vasa recta

a) Most of solutes diffuse back to the medullary interstitium b) Water diffuses from the interstitium to the blood of  vasa recta; maintain hyperosmotic gradient via: ►  Functions of vasa 1- Trapping solutes (NaCL and urea) in the renal medulla. 2- Removal of water reabsorbed from interstitium back to the blood.

Tubular  fluid  fluid leaving the leaving  the ascending loop ascending  loop of  Henle  Henle is hypotonic, while blood leaving the leaving  the ascending vasa ascending  vasa recta (medulla) is slightly hypertonic.

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kidney (Q & A)

Role of urea @ Urea contributes 50% of the medullary osmolality i.e. 500 mOsm/L . @ Thus plays an important role in the process of urine concentration: - A high protein diet increases the ability to concentrate the urine. - Protein deficiency impairs the ability to concentrate the urine. Mechanism In the Inner medullary portion of the collecting duct - Urea diffuses into the medullary interstitium to increase its osmolality. - Diffusion of urea is facilitated by ADH.

Role of ADH (a)

Collecting tubule: Collecting  tubule:

- ADH increase their permeability to H2 O  reabsorption of H2 O. - Diffusion of urea is facilitated by ADH. - Urea diffuses into the medullary interstitium to increase its osmolality (b)  ADH slows  ADH  slows

the flow the  flow in vasa recta:

by acting on the efferent arterioles of the juxtamedullary nephrons. This increases the medullary osmolality by decreasing washout of the medullary solutes.

 ADH  increase (c)  ADH increase

efferent arteriolar  efferent  arteriolar resistance: resistance:

of the juxtamedullary nephrons so increases their filtration, this leading to more removal of sodium from the lumen of ascending limb to the surrounding interstitial fluid, further, raises the concentration of sodium ions in the medullary interstitium.

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Q. What is Urea & NaCl cycles in the renal tubules 1- NaCl cycles: NaCl is transported from ascending limb of both LH & vasa recta to the interstitium. It then passively diffuses into the descending limb of vasa recta (and may be also slightly into descending limb of LH), then is transported again from ascending limb and so on.

2- Urea cycle: First, it diffuses passively from medullary CD to the interstitium from which it diffuses passively to descending limb of vasa recta & LH, it is then passively transported from ascending limb of  vasa recta and from medullary CD to the interstitium again and so on.

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Q. List different Disorders of urinary concent (A) Diabetes insipidus 1. Central DI: Decreased ADH secretion secretion due to lesion of posterior pituitary. pituitary. 2.  Nephrogenic DI: Congenital defect in V 2 receptors in the collecting duct.

(B) Impairment of the countercurrent mechanism  As in chronic renal failure → damage of renal medulla → the development of hyperosmolality hyperosmolality in medulla is poor  → loss of concentrating power  → iso-osmotic urine (as that of plasma) 300mosmol. & fixed specific gravity.

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kidney (Q & A)

Q. Describe different types of Diuresis Diuresis is an increase in the rate of urine output.

H2O diuresis

Osmotic diuresis

Caused by drinking large amount of water of hypotonic fluid. It begins after 15 min and reaches its maximum in 40 min. Mechanism; Mechanism; increase H2 O intake  decrease Osmotic. Pr  decrease  ADH  decrease facultative H2 O reabsorption i.e. Urine large volume and hypotonic. Caused by the presence in filterate of large quantities of un-reabsorbable solute e.g. glucose (DM) or mannitol. Mechanism; Mechanism; unreabsorbable solute in PCT decrease obligatory H2O reabsorption  decrease Na+ concentration in tubular fluid  decrease osmolarity of medullary interstitium  decrease facultative H2O reabsorption. - Urine: large volume and isotonic or hypertonic.

Pressure diuresis

Increase in arterial blood pressure leads to: - ↑ GFR. - Inhibition of rennin angiotensin system → ↓ renin and angiotensin II production. - ↑ Hydrostatic pressure in peritubular capillaries which → increase Na+ & H 2 O excretion.

Diuretic drugs

Thiazides: Thiazides: inhibit Na reabsorption in DCT.  Aldosterone inhibitors: inhibitors : (Potassium-sparing diuretics) inhibit Na-K exchange in DCT and collecting tubules  decrease serum Na and increase serum K+. Carbonic anhydrase inhibitors e.g. acetazolamide (Diamox). It inhibits carbonic anhydrase enzyme → decrease H+ secretion → decrease Na+ and HCO 3 - reabsorption in PCT and increase K+ secretion in DCT → increase Na+, HCO 3 - & K+ excretion in urine. May lead to acidosis. Loop diuretics e.g. frusemide (lasix): inhibit Na-K-2Cl cotransporters in the thick ascending limb of loop of Henle. Results:

↑ excretion of Na+, K+ & Cl- in urine. ↓ solute concentration in MI→↓ osmolality of medullary interstitium →↓ H 2 O reabsorption from CD → marked diuresis.

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kidney (Q & A)

Q. Describe Kidney function tests  Assessment of Renal plasma Flow

by PAH clearance - PAH is freely filtered and secreted but not reabsorbed. - The clearance of PAH from the blood is, only, almost complete if the blood concentration is low. But a low concentration concentration makes chemical analysis is difficult. - To overcome this difficulty, a derivative of PAH, radioactive iodine PAH may PAH  may be used. The concentration of this substance in blood and urine is estimated by determination of  its radioactivity.

Inulin clearance

 Assessment of Glomerular Filtration

Creatinine clearance

- Inulin is: freely filtered in glomeruli, not reabsorbed and not secreted, - measurement of GFR with inulin is inconvenient because inulin is not a normally occurring body substance and method for its measurement is difficult and time consuming. is the suitable method for routine use Easy to measure Endogenous substance.

Specific gravity of urine

Urine analysis

Urine specific gravity reflects the power of the kidney to concentrate and dilute urine Under normal conditions the specific gravity of urine varie  between 1.015-1.025. Patient is deprived of water overnight and the specific gravity, in the Water concentration morning specific gravity should normally be more than 1.020. In cases of severe renal damage specific gravity is fixed at 1.010.

test Water dilution test

 Assessment of Tubular Function

Imaging studies Blood analysis

Glucose tubular maximum Para-amino hippuric acid tubular maximum

The patient is given 1.5 liters of water in the morning. Urine is passed every hour for 4 consecutive and specific gravity is measured in every specimen. The specific should be less than 1.005. Impairment of water excretion indicates renal insufficiency. The reabsorptive power of the tubule can be measured by Tm Glucose. Tm PAH = 375 mg/min

The secretory power of the tubules can be measured determining Tm PAH. It can be determined by increasing the level of PAH in the plasma above the concentration that can completely removed from plasma by one circulation through the kidney. Tm PAH = 80 mg/min Renal US, Renal CT and Intravenous pyelography. a) blood urea; urea; normal 20-40 mg/dL (nonspecific test) It varies with protein intake, liver diseases and renal perfusion. b) Plasma creatinine; creatinine; normal 0.6 – 1.5 mg/dL (more accurate).  All the above values are increased in renal insufficiency. c)  potassium ions: 3.5-5mEq/L. d) inorganic phosphate: phosphate: 3-4.5mg%. e) pH: e)  pH: art.blood 7.4, ven. Blood 7.35.

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Q. Define pH and mention 2 disturbance of pH 1 pH = log

--------

[H+]  As H+ ion concentration increases, pH decrease (more acidic) and Vice versa. Each unit change in pH leads 10 fold change in H+. pH: arterial blood = 7.4 Venous blood = 7.35 Venous blood is acidic than arterial blood, because acids are added to venous blood  . If pH of arterial blood below 7.4 = acidosis If pH of arterial blood above 7.4 = alkalosis. Below pH (6.8) or above (8) death occurs. occurs.

Q. what are the serious effects of pH disturbances 1) Changes in excitability of nerve and muscle cells: increase in H+ (acidosis) may lead to coma. Decrease in H+ (alkalosis) leads to convulsions. 2) H+ changes affect enzymatic activity which disturbs metabolism. 3) Changes in H+, influences potassium level in blood.

Q. What is the different Sources of H+ in the body. 1) Carbonic acid formation (volatile acid): cellular oxidation carbonic anhydrase CO 2 + H 2 O H 2 CO 3 2) Inorganic acids (non volatile) produced during break down of nutrients. 3) Organic acids: Resulting from intermediary metabolism e.g: fatty acids, lactic acid (during exercise).

N.B. More acid produced than bases in body. 

Q. how pH is Regulated 1) The chemical buffer systems: -  Act immediately (in seconds). - are the first line of defense against changes in [ H] 2) The respiratory mechanism of pH control : - acts at moderate rate (in minutes). - is the second line of defense against changes in [ H ] - Respiratory system control the pH of the body by: Controlling CO 2 level in the blood. 3) The renal mechanism of pH control : - acts at slow rate (in hours, or days) - is the third line of defense against changes in [ H ] - The kidneys control the pH of the body fluid by: 1)Excretion 1) Excretion of acid or alkalie. -  2)Controlling 2) Controlling HCO  3 level in the blood. - is the most potent acid-base regulatory regulatory mechanism.

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Q. Describe different Buffer systems  A buffer is a molecule that combines with or releases a H+. It is composed of weak acid and salt of its conjugate bases. The combination of all buffers determines the pH. ►Henderson- Hasselbalch equation: pH = pK + log 10 (salt)

(Acid)

► Role of buffers in regulation of acid-base balance: Buffer act within fraction of a second (immediate) to trap H+ temporarily until respiration and renal mechanisms act. They only minimize the change in pH .

►Types of chemical buffer systems: 1- Bicarbonate buffer system. 2- Phosphate buffer system. 3- Protein buffer system. a. Plasma protein. b. Haemoglobin

Bicarbonate buffer system Major ECF buffer   Advantage; ► Advantage; Its 2 components can be physiologically controlled. (HCO3 ) by kidneys and (H2 CO 3 ) by respiratory system. ►How does a buffer work : Bicarbonate buffer consists of a mixture of carbonic acid (H2 CO 3 ) and sodium bicarbonate, (NaHCO3 ), when a strong acid is acid is added to the same buffer  e.g: HCl (strong acid) + NaHCO3 → H 2 CO 3 (weak acid) + Na Cl when a strong base is added to the same buffer: e.g: NaOH (strong base)+ H2 CO 3 → NaHCO 3 (weak base) + H2 O Therefore no marked change in the pH. Phosphate buffer system - It is a mixture of basis phosphate HPO4 and acid phosphate H2 PO 4 . - Its concentration is high in ICF and tubular fluid (DCT). Haemoglobin buffer  It plays an important role in CO 2 2  buffering . It has 6 times the buffering power of plasma protein because it is present in larger amount.

Q. Describe role of respiration in pH regulation Respiration controls pH via controlling blood PCO2 .  A decrease in pulmonary ventilation results in an increase in PCO2 and (H+). Mechanism of respiratory control of pH acidosis, ++ (H+) stimulates respiratory centers via peripheral chemoreceptors  ☺ In metabolic acidosis, hyperventilation   PCO 2  -- carbonic acid  -- (H+) . alkalosis, the reverse occurs. ☺ In metabolic alkalosis,

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kidney (Q & A)

Q. Describe role of kidney in pH regulation The kidneys control the pH of the body fluid by: by: a. Modifying H secretion. b. Modifying HCO 3 reabsorption. In alkalosis 1) kidney decrease H secretion leading to decrease H excretion in urine. 2) incomplete reabsorption of filtered HCO3.

(1)

In acidosis 1) increase H secretion and H excretion in urine. 2) reabsorption of all of the filtered HCO3. 3) addition of new HCO3 to the plasma.

Reabsorption of essentially all of the filtered HCO 3  3 

(2) Secretion of H + :  in urine by mechanism; ►mechanism; H+ is secreted in all parts of renal tubule except the descending and ascending thin limbs of loop of  Henle, for each H+ ion secreted, one bicarbonate ion is reabsorbed. Site H. Secretion 1. PCT 85% 2. Thick ascending loop of Henle 10% 3. DCT and collecting tubule 5% ► Mechanism of H+ secretion A) In PCT, LH and initial part of DCT: - Most of H+ is secreted by secondary active transport . - It is Na dependent. - Antiport carrier at luminal border bind Na and H. - Also, in PCT and LH, potassium LH, potassium can be reabsorbed in exchange for hydrogen. hydrogen. B) In late part of DCT and CD: - Hydrogen is secreted by primary by primary active transport . - Intercalated cells in these segments secrete hydrogen by H+ pump. - Also, in late DCT and CCD, hydrogen secretion is stimulated byaldosterone by aldosterone and both hydrogen and potassium compete for secretion. secretion.

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Buffering of H secreted by tubules: by 3 mechanisms (H+ is not left as free H+) by:

(1) H+ secretion against reabsorption of filtered HCO 3 cells: ►Inside tubular cells: CO 2 + H 2 O CA H 2 CO 3  H 2 CO 3  H+ + HCO 3 . - H+ is secreted in the tubular lumen in exchange for filtered Na+. - HCO 3 formed inside the cell moves to the blood. ►In the lumen: H+ (secreted) + HCO 3 (filtered)  H 2 CO 3 (CO 2 + H 2 O). CA CO 2 diffuses into the cells.

(2) Phosphate buffer: Titrable acid= urinary phosphate buffer that binds to H+ secreted. ►Mechanism of formation of titratable acid. Site: Distal tubules and collecting ducts. ►Site: cells: ►In the tubular cells: CO 2 + H 2 O H 2 CO 3  H+ + HCO 3 . CA - H+ is secreted into the tubular lumen bind with a titratable acid HPO4 - to form H2 PO 4 which is excreted in urine. - HCO 3 is added to the blood to form NaHCO3 .

(3) formation and secretion of ammonia:  Ammonia (NH 3 ) is generated from glutamine NH 3 acts as a H+ acceptor, it combined with H+. The resulting NH 4 ion is lipid insoluble i.e. cannot diffuse back out of the tubular lumen. This is called diffusion trapping , NH 4 is excreted in urine and HCO3 is returned to the blood.

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kidney (Q & A) +

Factors affecting (H  ) secretion in the kidney 1- PCO 2 : When PCO2 is high (respiratory acidosis), more intracellular HCO3 - is available and vice versa. 2- K+ concentration: concentration: When it increases, H+ secretion decreases since both compete for secretion in DCT & CCDs. 3- Carbonic anhydrase: anhydrase: When carbonic anhydrase is inhibited, acid secretion is inhibited. 4- Aldosterone: Aldosterone: enhances tubular reabsorbtion of Na + and increases K+ and H+ secretion.

Q. Mention detereminants of Acid-base state  pH depends  pH  depends on the ratio 1- pH values (7.35 to 7.45). 7.45). 2- PCO 2 ; (35 to 45 mmHg mmHg). 3- (HCO 3 ) ; i.e. alkali reserve (22-28 m Eq/Litre).  Acid- base disturbance is caused primarily by change in HCO3 or PCO 2 system This disturbance is corrected (compensated) by changes in the Second system or both systems to that: - The ratio (HCO 3 )/ PCO 2 and in turn pH returns to normal. - However, (HCO 3 ) and PCO 2 are both increase or decrease.

Q. Discuss different forms of acid-base disturbances  pH depends on the ratio  Acid-base state is determined by 3 measures 1- pH values (7.35 to 7.45). 7.45). 2- PCO 2 ; (35 to 45 mmHg mmHg). 3- (HCO 3 ) ; i.e. alkali reserve (22-28 m Eq/Litre).  Acid- base disturbance is caused primarily by change in HCO3 or PCO 2 system This disturbance is compensated by changes in the Second system or both systems to that: - The ratio (HCO 3 )/ PCO 2 and in turn pH returns to normal. - However, (HCO 3 ) and PCO 2 are both increase or decrease. Respiratory acidosis Respiratory alkalosis hypoventilation leading to CO2 accumulation in

Causes

blood leading to H2CO3 formation (acidosis). lung disease. depression of the respiratory center  respiratory muscle disorders.

decreased pH of arterial blood. Increased CO2 Increased CO2 of arterial blood. Normal HCO3 of arterial blood. Increased after Increased after compensation.

hyperventilation leading to CO2 loss from the blood leading to decreased H2CO3 formation

characters

systems: take up additional compensation - Chemical buffer systems: H. - Kidneys: 1) Increase in bicarbonate reabsorption. 2) Increase excretion of H+ (more acidic urine) leading to increase titrable acid (NaH2 PO 4 ) excretion. 3) Increased ammonia excretion in urine.

(alkalosis). Fever, Anxiety  O2 lack  Psychic hyperventillation increased pH of blood. decreased  CO2 of arterial blood. Normal HCO3 of arterial blood. decreased after decreased after compensation. - Chemical buffer systems liberate H. - Kidneys: - Decrease reabsorption of  HCO 3 and is excreted in urine (alkaline urine) - Decreased excretion of H in urine in the form of titrable acid (NaH 2 PO 4 ) and, ammonium salts.

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kidney (Q & A)

metabolic acidosis

Metabolic alkalosis

1) Severe diarrhea Causes 2) Diabetes mellitus 3) Strenuous exercise 4) carbonic anhydrase inhibitor. 5) In severe renal failure (uremia) decreased pH of arterial blood. characters decreased HCO3 of arterial blood. Normal CO2 of arterial blood. decreased  after compensation.

- Ingestion of alkaline drugs - vomiting of acidic gastric  juices.

increased pH of blood. increased HCO3 of arterial blood. normal CO2 of arterial blood. CO2 increased  after  compensation. - Chemical buffers systems. -The respiratory: hypoventilation - Kidneys: decrease H excretion in and increase HCO3 excretion

- Chemical buffer system. compensation - Respiratory: hyperventilation - renal mechanism : excretes more H and conserves more HCO3.

Lab Disorder

 

changes

pH

2

PCO  HCO  3

Respiratory acidosis Metabolic acidosis

--

++

N or ++

--

N Or --

--

Respiratory alkalosis

++

--

N or --

Metabolic alkalosis

++

N Or ++

++

Q. Describe how disturbance in ECF K is the cause of ACID – BASE disturbances - K+ and H+ concentration in the ECF parallel each other. - Potassium depletion (hypokalaemia) produces alkalosis and hyperkalaemia produces acidosis: because when K+ decrease, H+ replaces it inside cells leads to intracellular acidosis which occurs also in tubular cells of the kidney which increases H+ excretion in urine and HCO3 - reabsorption causing alkalosis. Conversely when K+ increases (hyperkalaemia) this causes increased K+ excretion (because both K+ and H+ are secreted in exchange with Na+ and compete for the available Na+ in the tubular fluid, H+ secretion is inhibited leading to extracellular  acidosis.

cel

cel

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kidney (Q & A)

Q. What is the Anion Gap  Definition It is the difference between the sum of the concentrations of the major plasma cations and the major anions. The anion gap = [Na+ + K+] – [Cl- + HCO3-]. 16 mEq/L.  Normal value

Sometimes K+ is omitted from calculation and the anion gap = 12 mEq/L.  Importance In metabolic acidosis, serum HCO3 - decreases. Thus, concentration of another anion must increase to maintain electroneutrality. This anion can be chloride or other unmeasured anions. The anion gap is increased  If concentration of other unmeasured anions is increased as in metabolic acidosis due to renal failure, lactic acidosis and diabetic ketoacidosis. The anion gap is normal  If concentration of chloride increased (hyperchloremic acidosis) as due to ingestion of NH4 Cl or carb carbon onic ic anhy anhyddras e inhi inhibi bito tors rs..

Q. Describe Innervation of the urinary bladder Parasympathetic 

Origin Effects

Sympathetic 

Origin

Effects Origin Pudendal nerves Effects

 Arises from lateral horn cells of 2nd, 3rd, 4th sacral segments of spinal cord, reach the bladder through pelvic nerves. 1- Contraction of bladder wall. 2- Opening of internal urethral sphincter.  Arise from lateral horn cells of upper 3 lumbar segments of  spinal cord, reach the bladder through lesser splanchnic nerve. 1- Relax the bladder wall  2- Closure of the internal urethral sphincter  3- Transmit pain sensation through sensory fibers. 4- Vasoconstriction.  Arise from anterior horn cells of 2nd, 3rd, 4th sacral segments of spinal cord. innervate and control voluntary skeletal muscle of external  urethral sphincter.

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kidney (Q & A)

Q. Discuss Mechanism of Micturition 1- Filling of the bladder. 2- Micturition reflex: is a spinal autonomic reflex. It is inhibited or facilitated by higher centers in the brain.  Bladder filling  The bladder can accommodate large volumes of urine without much increase in intravesical pressure until the bladder is well filled due to La Place’s Law which states that the pressure in spherical viscous equals twice wall tension (2T) divided by its radius (r). P = 2T  r   As urinary bladder fills, T & r both increase and IVP increases only slightly but at a certain volume (400  ml), T increases markedly and IVP rises sharply.

Cystometrogram (Pressure -volume relationship during bladder filling) a plot of the intravesical pressure against the volume of urine in the bladder. (1)  At intravesical pressure O , there is no urine in the bladder. (2) Segment la; pressure rises to 5-10 cm water by 50 ml of urine has collected. (3) Segment Ib; small additional rise in pressure with further increase in volume to200-300 to200-300 ml . This is explained by laplace law   As the bladder filled with urine, the tension in wall rises but so does the radius. Therefore, the pressure increase is slight until the bladder is relatively full i.e. no increase in Radius. (4) Segment II; sharp rise at a volume of 400 ml. The first urge to void is felt at a volume of 150 ml and marked sensation of fullness at volume of 400 ml.

 Micturition reflex  Stimulus; Volume of urine that initiates micturition reflex is 300-400 ml. ►Stimulus; ►Receptor ; stretch receptors in bladder wall.  Afferent; pelvic parasympathetic. ► Afferent; ►Centre; S 2 – S 4 . ►Efferent ; pelvic parasympathetic effectors; ►Response and effectors; Detursor muscle: contraction. Internal urethral sphincter: relaxation.

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 Higher control of micturition reflex  The reflex is controlled by facilitatory and inhibitory higher centres. ►Faciltatory centres : a) Pontine centres B) Post hypothalamus. Midbrain. ►Inhibitory centres : The higher centres exert final control of micturition 1- They partially inhibit the reflex except when except when micturition is desired. 2- They can prevent micturition by contraction of external urethral sphinct. 3- When it is time to urinate, the cortical areas ; - facilitate the sacral centre to initiate micturition reflex. - Inhibit thé external urethral sphincter.

Q. List different Abnormalities of Micturition A) Atonic bladder  Damage of the afferent, efferent efferent nerves,or damage of spinal Micturition centre. Manifested by retention with overflow . B) Automatic bladder  Due to complete transection of spinal cord above sacral region. Manifested by: bladder empties reflexely as soon as it is filled to critical capacity, as in infants.

Q. Explain how the micturition reflex can be voluntarily controlled. Because the external urethral sphincter is composed of skeletal muscle, its contraction and relaxation can be consciously controlled until the decision to urinate is made. This control is aided by nerve centers in the brain stem and cerebral cortex that can partially inhibit the micturition reflex. Nerve centers within the pons and hypothalamus function to make the micturition reflex more effective.

Q. Give short notes on acute & chronic renal failure Acute renal failure

Sudden (days or weeks) and reversible 1- Urine: Urine: Oliguria < 500 mL/day or even anuria. 2- Blood : Hyperkalaemia, metabolic acidosis, hypocalcemia and progressive increase in blood urea and creatinine. 3- Edema and hypertension. hypertension. Chronic renal failure

Develops over years and irréversible.  Azotemia; increase in urea, uric acid and creatinine (up to 10 times). (1)  Azotemia;  Anaemia; due to decreased erythropoietin secretion. (2)  Anaemia;  Acidosis: Inability to get rid of H and regeneration of HCO3 . (3)  Acidosis: (4) Urine osmolarity and specific gravity  approach that of glomerular filterate i.e. 290 mOsm and 1010 respectively due to loss of kidney ability to dilute or concentrate urine. Hypertension. (5) Hypertension. (6) Osteomalacia due to: a) Decreased production of 1,25 dihydroxy cholecalciferol. b) Increased blood PO4  Increase PTH  demineralization of bones.

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Treatment of renal failure (1) Kidney transplants (2) Dialysis a) Kidney machine (haemodialysis). b) Peritoneal Dialysis.

Q. List different Factors controlling ECF volume l) ADH: secretion: - Stimuli which increase ADH secretion: (1) decreased arterial pressure and (2) decreased blood volume (3) increased osmolarity. - When ECF volume decreases: decreases:  ADH causing increase in water reabsorption by distal tubules and collecting ducts of the kidney → increase ECF volume. - When ECF volume increases: increases: it causes inhibition of ADH secretion that increases water excretion and decreases ECF volume. 2) Role of the kidney: When ECF volume decreases leads to decrease in blood pressure which decrease glomerular  capillary pressure which decreases GFR and decreases the amount of Na+ filtered that leads to increase in tubular reabsorption of Na+ due to stimulation of aldosterone secretion. Conversely, when ECF volume increases which increases ABP and GFR that increase the amount of  filtered Na+ that inhibit release of aldosterone which increase urinary excretion of Na+ and water  causing decrease of ECF volume.

3) Renin-angiotensin-aldostero Renin-angiotensin-aldosterone ne system: When ECF volume decreases, decrease in blood pressure stimulates renin secretion from the juxtaglumerular apparatus of the kidney. renin ACE   Angiotensinogen Angiotensinogen angiotensin angiotensin I angiotensin II Angiotensin II causes: a. stimulates aldosterone and ADH secretion. b. stimulates thirst center. c. vasoconstriction. vasoconstriction. 4) Thirst mechanism: When ECF volume decrease: decrease: this stimulates thirst center in hypothalamus that leads to increase in water intake. 5) Volume receptors: Present in the atria and great veins near the heart. When ECF volume decreases, they send impulses to the hypothalamus causing reflex increase in sympathetic discharge with activation of renin-angiotensin system. 6) Atrial natriuretic peptide (ANP): i) inhibiting Na+ reabsorption in distal tubules. ii) increasing intracellular cGMP which inhibits Na+ transport. iii) inhibition of secretion of ADH and aldosterone.

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iv) inhibiting renin secretion and counteracting the effects of angiotensin II. v) increase in GFR through relaxing mesangial cells.

Q. Describe Renal Na Handling - 96% - 99% of the filtered Na is reabsorbed. - Na is actively reabsorbed in all portions of the tubule except in the thin ascending part of loop of  Henle. - Most Na+ is reabsorbed with Cl-. Some Na+ is reabsorbed in exchange for H+ secretion. In distal tubules, a small amount reabsorbed in exchange with K+ secretion. (1) Proximal tubule; 65-67% is reabsorbed by primary active transport.

(2) Loop of Henle and early distal tubule a) Thin descending limb; reabsorbs water, Na is not reabsorbed . b) Thin ascending limb; NaCL is passively reabsorption by concentration gradient. c) Thick ascending limb and early distal tubule; tubule; + + 25% of the filtered load of Na , K and CL are reabsorbed by cotransport mechanisms, that cotransport one Na+, one K+ and two CL from the lumen into the cells. It plays a role in urine concentration. (3) Late distal tubule and collecting duct - 8% of filtered Na+ is reabsorbed accompanied by CL. - under the effect of aldosterone & ANP.

 Regulation of Na excretion (1) Glomerulo tubular balance Definition; ++ GFR  ++ reabsorption of solutes and, in turn, H2 O. Site; PCT (main site) and loop of Henle. It is prominent for Na, the renal tubules reabsorb a constant percentage of the filtered Na rather than a constant amount. Importance: It prevents overloading of distal segment when GFR is increased. It prevents losses of Na+ and water in urine. (2) Transtubular Physical factors. - Low hydrostatic pressure and high oncotic pressure in the peritubular capillaries promote Na+ reabsorption.

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(3) Hormonal control; a) Aldosterone a) Aldosterone:: act on DCT to increase Na reabsorption in exchange with K+ or H+. b) Angiotensin b) Angiotensin II: most powerful Na+ retaining hormone by direct action of PCT and via aldosterone. c) Atrial c) Atrial natriuretic peptide (ANP): (ANP) : + Inhibiting Na reabsorption in distal tubules. (4) Sympathetic stimulation; decrease Na+ excretion via * increase Na reabsorption in PCT and thick ascending limb. * increase Renin secretion  increase angiotensin II. * vasoconstriction of afferent arteriole.

Q. Give short notes on tubular handling of K, Ca & Ph. Tubular handling of K+ K+ reabsorption 1- PCT: Reabsorption of 80% by 2ry active transport. 2- Thick ascending limb of loop of Henle : Reabsorption of 20%. Actively cotransported with Na & CL by cotransport system which transports 1 Na +, 1 K + and 2 Cl-. K+ secretion in distal nephron under the effect of aldosterone. -  Na moves into interstitium and K + moves into the cell. - K competes with H for the carrier in the distal tubules.

Factors affecting K+ secretion and excretion +

1. Dietary K  intake: intake: + increase K  intake increase K + secretion increase K + excretion. 2. Aldosterone hormone : increases K + secretion and excretion in urine. 3. Na+ reabsorption: reabsorption: when amount of Na + reaching the distal tubule increase increase K + secretion increase K + excretion 4. Hydrogen secretion: secretion : since both H+ and K + compete for secretion. Increase of H + secretion (as in acidosis) decrease K + secretion and vice versa. →

→

→

→

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Ca Handling Only plasma Ca ++ not bound to plasma protein (60%) are filtered in kidney, 99% of filtered Ca++ are reabsorbed by renal tubules. 1. PCT; 65%.

2. Loop of Henle; (thick ascending limb) 25-30%.  In PCT & LH, Ca +2 reabsorption occurs secondary to Na + reabsorption by ry 2 active transport or passive reabsorption down electrochemical gradient.

3. DCT and collecting tubules; 4-9% are actively reabsorbed. Parathyroid hormone stimulates Ca ++ reabsorption. Factors increase Ca ++  reabsorption   parathyroid hormone, active vitamin D, chronic metabolic alkalosis.

Phosphate Handling by renal tubules Phosphate is reabsorbed mainly in PCT (80%), Small amount is reabsorbed in thick  ascending limb of LH, DCT & CD. Secondary active transport with Na. controlled by parathyroid hormone.