exam 2 lecture 23-28

Question 1

functions of kidney

Answer 1

• Regulation of the water and electrolyte content of the body.
• Retention of substances vital to the body such as protein and glucose
• Maintenance of acid/base balance.
• Excretion of waste products, water soluble toxic substances and drugs.
• Endocrine functions
  
  • Metabolic functions

Question 2

four homeostatic functions of the kidney

Answer 2

1. Excretion of the metabolic waste products
2. Preservation of important substances
3. Regulation of the volume and composition of the extracellular fluid
4. Regulation of the acid-base balance

Question 3

what are 3 endocrine functions of the kidney

Answer 3

•Erythropoietin – regulates red blood cell production – key in fighting anemia

• 1,25(OH)2 vitamin D3 (calcitriol) – regulates Ca and phosphate metabolism – important for the bone health
• Renin, bradykinins and prostaglandins – regulation of systemic and local (renal) hemodynamics – key factors in arterial hypertension

Question 4

•___ – regulates red blood cell production – key in fighting anemia

Answer 4

Erythropoietin

Question 5

•1,25(OH)2 vitamin D3 (___) – regulates Ca and phosphate metabolism – important for the bone health

Answer 5

calcitriol

Question 6

•___ – regulation of systemic and local (renal) hemodynamics – key factors in arterial hypertension

Answer 6

Renin, bradykinins and prostaglandins

Question 7

•Participation in production of the glucose pool. Key site for glycolysis, gluconeogenesis, and ___

Answer 7

proteolysis

Question 8

filtration occurs where in the kidney?

Answer 8

cortex

Question 9

re-absorption of water mainly occurs where in the kidney?

Answer 9

medulla

Question 10

bladder expels urine from the body by ___

Answer 10

micturition

Question 11

the two functions of the tubule of the nephron are?

Answer 11

reabsorption (from tubule back into the blood)

secretion (from blood into nephron)

Question 12

The kidney is unique as it has two capillary beds arranged in series, the ___capillaries which are under high pressure for filtering, and the ___ capillaries which are situated around the tubule and are at low pressure.

Answer 12

glomerular

peritubular

Question 13

Juxtaglomerular apparatus

Answer 13

Afferent arteriole + Efferent arteriole + juxtaglomerular (JG) cells + Macula densa

Question 14

what are the cells that measure flow of urine and tells the afferent arteriole to change speed

Answer 14

macula densa

Question 15

flow of blood in the kidney

Answer 15

Blood vessels:

1. Renal artery
2. Interlobar arteries
3. Arcuate arteries
4. Interlobular arteries
5. Afferent arterioles
6. Glomerular capillaries
7. Efferent arterioles
8. Peritubular capillary plexus.
9. Vasa recta

Parallel venous system

Question 16

red blood cell cast

Answer 16

RBC put into water will fill with water, explode and turn inside out

Question 17

•Filtration takes place through the semipermeable walls of the glomerular capillaries which are almost impermeable to ___ and large molecules.

Answer 17

proteins

Question 18

The filtrate is thus virtually free of ___ and has no cellular elements

Answer 18

protein

Question 19

•The glomerular filtrate is formed by squeezing fluid through the ___.

Answer 19

glomerular capillary bed

Question 20

•The driving hydrostatic pressure is controlled by the afferent and efferent arterioles, and provided by ____.

Answer 20

arterial pressure

(kidney close to aorta= high blood pressure)

Question 21

structure of glomerular capillary wall

Answer 21

1. capillary endothelium – single layer of cells forming numerous fenestrae (windows),
2. glomerular basement membrane – acellular structure composes of glycoproteins (collagens, etc.), which is arranged in 3 layers (lamina rara externa, interna, and lamina densa),
3. visceral endothelium – podocytes with slit diaphragm (proteinous membrane contains nephrin, other proteins)

Question 22

whole in the capillary endothelium to allow small molecules through

Answer 22

fenestrae

Question 23

glomerular basement membrane is made of 3 layers of ___

Answer 23

glycoproteins

Question 24

what are the three layers of the glomerular basement membrane?

Answer 24

lamina rara externa

interna

lamina densa

Question 25

visceral endothelium of the glomerular capillary wall are made of \_\_\_

Answer 25

podocytes

Question 26

\_\_\_ hold podocytes together

Answer 26

slit diaphragm | (proteins)

Question 27

what is the opposing force for in the glomerulus?

Answer 27

**oncotic pressure** (pressure of water of area with no proteins in the nephron to pressure of area with alot of proteins in the afferent arteriole) **P_BS hydrostatic pressure**: from the bowman's space (very small)

Question 28

\_\_\_ •Mostly determines the rate of filtration as well of the tubular fluids/urine flow to renal pelvis

Answer 28

P_GC hydrostatic pressure in the glomerular capillary

Question 29

hydrostatic pressure in the glomerular capillary is determined by blood input from ___ arterioles and tonus of ___ arterioles

Answer 29

afferent efferent

Question 30

P_GC is the primary target of regulatory mechanisms that control \_\_\_

Answer 30

GFR

Question 31

∏_GC

Answer 31

plasma oncotic pressure * Is determined by difference of protein concentrations between blood plasma and glomerular filtrate * Is NOT a primary target of regulatory mechanisms that control GFR * As blood travels through the glomerular capillary, a large proportion of the fluid component of the plasma is forced across the capillary wall by **P_GC**. Meanwhile, most of the plasma proteins are retained in the capillary lumen. Therefore, the plasma oncotic pressure (**∏_GC**) increases significantly along the capillary bed.

Question 32

\_\_\_ •Is determined by difference of protein concentrations between blood plasma and glomerular filtrate

Answer 32

plasma oncotic pressure

Question 33

as blood travels through the glomerular capillary what happens to oncotic pressure?

Answer 33

**increases** fluid leaves, proteins stay therefore the pressure of protein to not protein increases

Question 34

what can cause hydrostatic pressure in the bowman's space (P_BS) to increase?

Answer 34

obstruction- nephrolithiasis, tumors, etc

Question 35

•\_\_\_ - "sieve" function –– contributes to the co-efficient of ultrafiltration (**Kf)** along with filtration surface

Answer 35

Permeability

Question 36

what things can freely filter out of glomerulus

Answer 36

•water, small cations (Na⁺, K⁺), small anions (Cl^-), glucose

Question 37

what things are poorly filtered by the glomerulus?

Answer 37

•polypeptides (proteins), except in pathological conditions (proteinuria).

Question 38

what factors affect permeability of polypeptides through the glomerulus?

Answer 38

* Size. Proteins the size of plasma albumins or larger are not efficiently filtered compared to smaller peptides * Shape. Long flexible proteins are filtered more efficient than globular proteins. Charge. Positively charged (cationic) polypeptides are filtered more efficiently than negatively charged (anionic) molecules. For example, cationic form of albumin is filtered 300 times more efficiently than native (uncharged) albumin

Question 39

cations or anions can filter more easily?

Answer 39

**Positively charged (cationic)** polypeptides are filtered more efficiently than negatively charged (anionic) molecules

Question 40

\_\_ is loss of negative charge on the glomerular membrane and loss of its integrity

Answer 40

glomerulonephritis happens during proteinuria

Question 41

list +, - and neutral in how easily they get across glomerulus

Answer 41

cation (positive) easiest neutral anions (negative) hardest

Question 42

•The kidney normally maintains the ___ at a relatively constant level despite changes in systemic blood pressure and renal blood flow.

Answer 42

GFR

Question 43

•The GFR is maintained within the physiologic range by what two factors?

Answer 43

**Systemic factors** (renal modulation of systemic blood pressure and intravascular volume) **Intrinsic factors** (control of renal blood flow, P_GC, and K_f)

Question 44

GFR is maintained by intrinsic factors such as \_\_

Answer 44

control of renal blood flow, P_GC and K_f

Question 45

juxtaglomerular apparatus contains __ that senses change in pressure and trigger the renin-angiotensin-aldosteron system

Answer 45

extraglomerular mesangial cells

Question 46

extraglomerular mesangial cells (Juxtaglomerular cells) trigger ___ system

Answer 46

renin-angiotensin-aldosteron system

Question 47

\_\_\_ is a polypeptide hormone, produced by specialized cells of the wall of the afferent arteriole (JG cells).

Answer 47

renin

Question 48

Release of renin is stimulated by a ___ in renal perfusion (usually due to systemic \_\_\_)

Answer 48

decrease hypotension

Question 49

•Renin catalyzes the conversion of peptide ____ (produced by liver) into angiotensin I

Answer 49

angiotensinogen

Question 50

•Angiotensin I is further converted to angiotensin II by \_\_\_

Answer 50

angiotensin-converting enzyme (ACE, located primarily in the cells of vascular endothelium in lungs, kidney, etc).

Question 51

how does angiotensin II work

Answer 51

* _directly_ - constricts arterial blood vessels to increase systemic blood pressure and renal perfusion pressure * 2 _indirectly_ - stimulates the release of * 2a - the mineralocorticoid steroid hormone ***aldosterone*** from the adrenal gland * 2b - polypeptide hormone ***vasopressin*** (a.k.a. ***ADH, anti-diuretic hormone***) from the pituitary gland. * Both these hormones retain electrolytes and water from excretion, thus increasing overall intravascular circulating volume and elevating systemic blood pressure and renal perfusion.

Question 52

renin pathway

Answer 52

low renal perfusion causes release of **renin** **renin** converts **angiotensinogen** to **angiotensin I** in the liver angiotensin I and **ACE**(angiotensin-converting enzyme) → **angiotensin II** (in lungs and kidneys) angiotensin II triggers vasoconstriction everywhere except the renal afferent arterioles where it produces prostaglangin E2 and I2 that causes vasodilation and release of **aldosterone** from the adrenal gland and **anti-diuretic hormone** from the pituitary **these will retain electrolytes and water which will increase blood pressure and renal perfusion**

Question 53

angiotensin II triggers the release of this mineralocorticoid steroid hormone \_\_\_from the adrenal gland

Answer 53

***aldosterone***

Question 54

angiotensin II causes the release of this polypeptide hormone ___ from the pituitary gland.

Answer 54

***vasopressin*** (a.k.a. ***ADH, anti-diuretic hormone***)

Question 55

what does angiotensin II do to renal afferent arterioles?

Answer 55

angiotensin II triggers vasoconstriction everywhere except the renal afferent arterioles where it produces prostaglangin E2 and I2 that causes vasodilation

Question 56

constriction of the afferent arteriole does what to pressures?

Answer 56

increases renal vascular resistance (thereby reducing RPF) and decreases the intraglomerular pressure and GFR **decreases P_GC, GFR and RPF (renal plasma flow)**

Question 57

constriction of the efferent arteriole does what to pressures?

Answer 57

increases PGC and GFR decreases Renal plasma flow

Question 58

prolonged increased blood pressure will do what to kidneys?

Answer 58

damage vascular walls → stenosis which will decrease renal perfusion and increase renin which increases blood pressure and repeat

Question 59

enalapril is a \_\_\_

Answer 59

ace inhibitor decrease hypertension in the renal arteries by stopping angiotensin I from turning into angiotensin II and preventing increase in blood pressure

Question 60

The intrarenal pressure distal to stenosis should be lower than the arterial pressure. As a result, lowering systemic blood pressure AND preventing ability of AII to compensate for that by constricting the efferent arteriole (see B) can dramatically decrease GFR and may lead to an \_\_\_

Answer 60

acute renal failure.

Question 61

two intrinsic factors regulating GFR

Answer 61

* The myogenic reflex * The tubulo-glomerular feedback.

Question 62

myogenic reflex

Answer 62

* Glomerular arterioles respond to changes in arteriolar wall tension. * As a result, there is an immediate **arteriolar constriction** in response to an increase in this wall tension (usually caused by **systemic hypertension)**. * Conversely, a decrease in arteriolar wall tension results in virtually immediate arteriole dilation. * **These dilations and constrictions regulated the resistance to blood flow in the afferent arteriole and contribute to maintenance of renal blood flow and GFR at constant levels despite marked alterations in the blood pressure in renal artery** .•The reflex is independent of renal innervations but might be influenced by levels of prostaglandins and NO.

Question 63

tubulo-glomerular feedback

Answer 63

**macula densa** found in the distal portion of the thick ascending limb of the loop of henle are sensitive to an increase of tubular flow rate and will cause afferent arterioles to decrease the GFR * Macula densa cells are sensitive to an increase in the tubular flow rate (which is dependent on P_GC within the same nephron). Such an increase leads to a decrease in the filtration rate of glomerulus of the same nephron by a yet poorly characterized mechanism. * As a result, this system would check the single nephron GFR to avoid speeding in tubular flow, which may lead to overwhelming the capacity of the tubule to re-absorb water and solutes.

Question 64

how to measure GFR

Answer 64

**•****Cx = (Ux x V)/Px** * Cx – the volume of plasma cleared of substance X per unit time * Ux – urine concentration of substance X * V – volume of urine collected divided by the time period of collection * Px – plasma concentration of substance X

Question 65

In clinical practice, the GFR is one of the most important parameters of renal function. The GFR is being determined by the rate of clearance of the plasma of a particular substance. This rate is measured by the rate of elimination divided by the \_\_\_of the substance

Answer 65

plasma concentration

Question 66

when calculating GFR. The total rate of clearance of these compounds is the sum of the rates of filtration and secretion minus the rate of \_\_\_

Answer 66

re-absorption.

Question 67

what is an indicator substance of choice to measure GFR?

Answer 67

inulin (a xenobiotic) •Inulin is freely filtered by the glomerulus but is neither absorbed nor secreted by the renal tubular cells. **•****GFR = C_inulin = (U_inulin x V)/P_inulin** * where GFR, as well as C_inulin is in ml/min * U_inulin – the inulin concentration in a urine sample collected of a period of time T in minutes * V – volume of urine collected over a period of time T * P_inulin – the mean plasma inulin concentration during time T

Question 68

calculate GFR if P=1 mg/ml U= 100 mg/ml V= 1.25 ml/min

Answer 68

GFR= (U x V)/P (100 x 1.25)/1 **125 ml/min**

Question 69

in practice what is the most widely used indicator for GFR?

Answer 69

creatinine (can not be used for birds) (very good for dogs, some reabsorption for cats)

Question 70

•In veterinary medicine, the \_\_\_is better expressed on the basis of body weight or body surface area (in ml per min per kg/m2) because of the large variation in size of individual species

Answer 70

GFR

Question 71

why is creatinine clearance slightly overestimated in humans and felines

Answer 71

•Small amount of creatinine in felines and humans is secreted in the tubules (10%)

Question 72

Answer 72

GFR roughly = to % nephrons working creatine above 1.2 = kidney not working well

Question 73

If a substance X is almost completely cleared from renal plasma by one pass through the kidney as a result of filtration and secretion (as for p-aminohippuric acid), then the clearance of X will equal \_\_\_

Answer 73

renal plasma flow

Question 74

\_\_\_ refers to the fraction of renal plasma flow that is actually filtered by glomeruli

Answer 74

filtration fraction (FF) FF= GFR/RPF

Question 75

\_\_\_ is the rate of urinary excretion of a substance X divided by its rate of filtration

Answer 75

fractional excretion (FE) •FEX = (U_X x V) / (P_X x GFR)

Question 76

•This parameter is used to evaluate net secretion/re-absorption:

Answer 76

fractional excretion (FE) * FEX = (U_X x V) / (P_X x GFR) * If FE \> 1, there is net secretion of the indicator substance by the tubule * If FE \< 1, there is net re-absorption of the indicator substance by the tubule

Question 77

If FE \_\_\_, there is net secretion of the indicator substance by the tubule

Answer 77

\> 1

Question 78

•If FE \_\_\_, there is net re-absorption of the indicator substance by the tubule

Answer 78

\< 1

Question 79

15-year old male cat is listless, inappetent and thin. The cat has been drinking more water than usual lately, urinating large volumes, and vomiting frequently.

Answer 79

PUPD polyuria and polydipsia

Question 80

serum creatinine level is 8.7 mg/dL (normal 0.5-1.2) this is called \_\_\_

Answer 80

azotemia •Etiology could be pre-renal, renal or post-renal

Question 81

uremia

Answer 81

end result of chronic renal failure abnormal quantities of urine constituents in blood caused by renal disfunction polysystemic toxic syndrome that occurs as a result of abnormal renal function

Question 82

**History**. 3-year spayed female spaniel dog has not been eating well for several days and seems to tire easily. **Examination**. The dog seems bright and alert and is in good flesh. The only abnormality detected is slight pitting edema on the distal extremities. The left kidney is palpable and feels smooth and of normal size. Urinalysis yields normal result except for 3+ protein (normal negative to trace amount) and the presence of a few red blood cell casts. A complete blood cell count is normal and the only abnormality is low serum albumin levels of 1.5 g/dL (normal 2.3-4.3)

Answer 82

something is eating membrane of glomerulus and allowing proteins and RBC into the nephrons ## Footnote **proteinuria**

Question 83

proteinuria

Answer 83

* Pre-renal * Overload: hemaglobinuria, myoglobinuria, light chain in myeloma, * Functional: transient increased intraglomerular pressure (exercise, fever, seizures) Post-renal (traumatic or neoplastic hemorrhage or inflammation in the lower urinary tract) •Clinical problems of proteinuria: edema/anasarca + neprotic syndrome (proteinuria, hypoalbuminemia, hyperlipoproteinemia/hypercholesterolemia)

Question 84

\_\_\_\_ refers to disorders in which there is increased glomerular permeability to macromolecules

Answer 84

Nephrotic syndrome

Question 85

Nephrotic syndrome

Answer 85

refers to disorders in which there is increased glomerular permeability to macromolecules This increased permeability leads to a constellation of clinical findings including heavy proteinuria, hypoalbuminemia and edema diverse causes such as glomerulonephritis

Question 86

tubular ___ is a process where the direction of solute transfer is from the tubular lumen to the peritubular capillary plasma

Answer 86

**reabsorption**

Question 87

the opposite direction from the peritubular capillary plasma to tubular lumen is called tubular \_\_\_\_

Answer 87

**secretion**.

Question 88

what three things are re-absorbed 100%

Answer 88

glucose polypeptides potassium

Question 89

\_\_\_ •the percentage of a filtered substance that is ultimately excreted in the urine.

Answer 89

FER (fractional excretion rate)

Question 90

•FER is the net result of the tubular re-absorption and secretion. It is calculated as ratio of the ___ to plasma concentration (P) of the compound of interest divided per similar ratio of a reference compound (usually – creatinine)

Answer 90

urinary concentration (U) ## Footnote For the substance X : FER_x = (U_x/P_x)/(U_creatinine/P_creatinine) x 100%

Question 91

•represents the proportion of filtered substance X that is reabsorbed by the tubule.

Answer 91

FAR fractional re-absorption rate •FAR = 100% - FER For the substance X : FER_x = (U_x/P_x)/(U_creatinine/P_creatinine) x 100%

Question 92

how to calculate FAR

Answer 92

For the substance X : FER_x = (U_x/P_x)/(U_creatinine/P_creatinine) x 100% •FAR = 100% - FER

Question 93

where does most re-absorption take place?

Answer 93

proximal tubule (large brush border = increased surface area) the trans-cellular pathway, and the paracellular pathway.

Question 94

how does the proximal tubule move fluid

Answer 94

the trans-cellular pathway the paracellular pathway.

Question 95

the trans-cellular pathway of the proximal tubule

Answer 95

Substances are taken up from tubular lumen by the cells through apical plasma membranes – large surface area (brush border structure created by numerous microvilli) is available for this uptake. * Active transport that requires energy is supported by numerous mitochondria * Substances are passed into numerous capillaries of peritubular plexus (arrow)

Question 96

substances reabsorbed in the proximal tubule go where?

Answer 96

peritubular plexus

Question 97

para cellular pathway in the proximal tubule

Answer 97

Substances are reabsorbed through this pathway move from tubular fluid across the ***tight junctions*** (zonula occludens), a highly permeable structure, which attaches the cells of epithelial sheet to each other and forms the boundary between the apical and basolateral membranes. from there interstitial fluid → peritubular capillaries

Question 98

•*Paracellular transport occurs by passive diffusion (along concentration gradient) or by \_\_\_*

Answer 98

solvent drag Solvent drag is a mechanism, which is the entrainment of solute by the flow of water.

Question 99

starling forces

Answer 99

para-cellular pathway in the proximal tubules→ moving through tight junctions into the peritubular capillaries Blood in these capillaries has high **oncotic** pressure (due to loss of volume to filtrate and concurrent increase in protein concentration) and low hydrostatic pressure (due to low resistance of their walls). Both of these conditions are conducive to the movement of fluid and solutes from the interstitium **into the bloodstream.**

Question 100

3 ways to reabsorb in the proximal tubule

Answer 100

1. passive diffusion (Ca²⁺, Mg²⁺, Cl^-) 2. solvent drag (K⁺, Cl^-) 3. primary active transport (Na⁺) •Much of the transport of substances from the tubular fluid to the blood is driven by active transport of Na⁺.

Question 101

•Much of the transport of substances from the tubular fluid to the blood is driven by active transport of \_\_\_

Answer 101

Na⁺.

Question 102

solvent drag in the proximal tubule works for \_\_

Answer 102

reabsorption of K+ and Cl- Cl- also moves by passive diffusion

Question 103

passive diffusion in the proximal tubule is for \_\_\_

Answer 103

calcium, magnesiuma and Cl- | (Cl- also moves by solvent drag)

Question 104

active transport in the proximal tubule is for

Answer 104

reabsorption of Na+

Question 105

The ATP-dependent transcellular transport of Na⁺ in different tubular segments enables the formation of the \_\_\_\_

Answer 105

electro-chemical gradients

Question 106

Transport of Na⁺ drives the reabsorption of many other solutes including glucose, ___ amino acids, etc

Answer 106

phosphate,

Question 107

Na- K ATPase pump

Answer 107

This pump extrudes 3 Na⁺ ions from the cell into the interstitial fluid and takes up 2 K⁺ ions into the cell per one molecule of utilized ATP. results in increase in intracellular K⁺ followed by its outward diffusion via K⁺ channels. These events **polarize the cell (negative charge of the cell’s interior)** and form an electro-chemical gradient across the apical membrane this gradient facilitates movement of **Na+ from tubular fluid into the cell** via special Na+ transporters. Co-transport of glucose, amino acids, phosphate, sulfate and organic anions. Uptake of these substances allows them to move **trans-cellularly into the interstitial fluid and bloodstream by passive or facilitated diffusion.** With Na⁺ and other cations moving out of the lumen, specific concentration of **free Cl^- in the tubular fluid rises**, establishing an electrical and chemical gradient for Cl^- movement in the direction of interstitial fluid. **Tight junction** (zonula occludence) are highly permeable for Cl^- allowing its **re-absorption via paracellular pathway.**

Question 108

what happens to K after Na/K pump

Answer 108

Na/K pump results in increase in intracellular K⁺ followed by its **outward diffusion via K⁺ channels**. These events **polarize the cell (negative charge of the cell’s interior)** and form an electro-chemical gradient across the apical membrane

Question 109

the diffusion of K out of the cell create an electro-chemical gradient which triggers \_\_\_

Answer 109

This gradient facilitates movement of Na+ from tubular fluid into the cell via special Na+ transporters. **co-transport** of glucose, amino acids, phosphate, sulfate and organic anions. Uptake of these substances allows them to move trans-cellularly into the interstitial fluid and bloodstream by **passive or facilitated diffusion.**

Question 110

movement of Na+ causes Cl- to do what?

Answer 110

With Na⁺ and other cations moving out of the lumen, specific concentration of free Cl^- in the tubular fluid rises, establishing an electrical and chemical gradient for Cl^- movement in the direction of interstitial fluid. **Tight junction (zonula occludence)** are highly permeable for Cl^- allowing its re-absorption via paracellular pathway.

Question 111

transport maximum

Answer 111

there is a limit to the reabsorption of substances per time if the amount exceeds this rate then some will be left in the urine, (can not absorb fast enough) this is what happens with diabetes (normal Tmax= 2.1mmol/min for glucose- diabetic= 10 mmol/min)

Question 112

how do peptides get reabsorbed in the proximal tubule?

Answer 112

peptides get broken down into amino acids by brush border amino acids are **co-transported with Na+** and protons or bind to receptor and endocytosis into the cell

Question 113

how do hormones get reabsorbed in the proximal tubule?

Answer 113

Low molecular weight proteins including hormones are reabsorbed by **endocytosis** upon binding to their receptors on apical membrane. The receptor-protein complexes are internalized by **coated pits (CP)-mediated endocytosis** (into endocytic vesicles, EV) and directed to **endosomal-lysosomal system** (E-L) within the proximal tubule cells to undergo **proteolysis**. Resultant amino acids are transported to the interstitial fluid and returned to the bloodstream.

Question 114

what kind of organic ions are secreted into the proximal tubule?

Answer 114

too big to be filtered in the glomerulus so get excreted here These organic ions include * endogenous waste products including bile salts, oxalate, urates, hippurates, prostaglandins, epinephrine and other hormones, etc. * exogenous drugs or toxins including antibiotics (e.g., penicillin G), diuretics (chlorothiazide, furosemid), morphine and its derivates, some herbicides, etc

Question 115

tubular secretion is by \_\_\_

Answer 115

passive or active secretion

Question 116

what are some things secreted in the primary tubule?

Answer 116

**anions** urate, penicillin, salicylate, phenobarbital, probenecid **cations** creatinine (felines), cimetidine, morphine

Question 117

Veterinary importance of proximal tubular secretion:

Answer 117

* monitoring function of the tubule * prescribing medicines that are secreted to concentrate in urine and act selectively in urinary tract. For example, antibiotics against urinary infections; diuretics, etc * determination of poisoning with herbicides, other toxins * performance enhancing substances testing (e.g. in equestrian sports) * in birds – this is the primary mechanism of excretion of major protein metabolism end product – uric acid.

Question 118

the distal tubule are important for re-absorption of \_\_\_

Answer 118

Na+, K+ Cl-, Calcium and Mg2+

Question 119

\_\_\_ exhibit poor permeability to water. Thus, re-absorption of ions in these segments leads to reduction in the osmolality of the tubular fluid

Answer 119

distal tubule (thick ascending limb of the loop of Henle and the distal convoluted tubule)

Question 120

\_\_\_ are able to reabsorb solutes against a high gradient

Answer 120

distal tubules (thick ascending limb of the loop of Henle and the distal convoluted tubule)

Question 121

\_\_\_ is where 35-40% of the filtered NaCl is reabsorbed – in excess of that of water

Answer 121

thick ascending loop of henle salt is reabsorbed but water is not, creates hypertonic (watery) solution

Question 122

explain re-absorption in the thick ascending loop of henle

Answer 122

Na/K pump pushes 2K into cell and 3 Na out into the interstitial space K leaves through diffusion into both urine and interstitial fluid loss of Na in the cell cause Na/K co transporter Cl into the cell. Cl leaves cell causing interstitial fluid to become more negative, this causes Mg,Ca, K and Na to be pulled through tight junctions (paracellular pathway) into interstitial fluid to balance charge

Question 123

where does this happen

Answer 123

thick ascending loop of henle (no brush border, basolateral border wavy)

Question 124

how does furosemid work

Answer 124

works in the thick ascending loop of henle diuretic inhibit Na,K,Cl co transporter from urine back into the blood this increase in salt in the urine causes water to flow from blood into urine. **this can causes drastic loss of K and needs to be supplemented by diet or infusion**

Question 125

what two major cell types are found in the collecting ducts?

Answer 125

principal intercalated cells

Question 126

what is the main function of the collecting duct

Answer 126

Intercalated cells are involved in K⁺ and Na⁺ re-absorption. Principal cells are involved in K⁺ secretion. •***_The ultimate rate of renal excretion of K_⁺ _and its concentration in the urine is determined by efficiency of these two mechanisms._***

Question 127

Intercalated cells are involved in\_\_\_re-absorption. Principal cells are involved in ___ secretion. ## Footnote where are these cells found?

Answer 127

K⁺ and Na⁺ K⁺ **collecting duct**

Question 128

intercalated cells

Answer 128

K and Na re-absorption * they have large numbers of mitochondria and intracytoplasmic vesicles. * they are mainly located in the **outer part of the medullary collecting ducts.** * they reabsorb K⁺ from the tubular fluid. * K⁺ is actively transported into the cell from the lumen by a **H⁺,K⁺-ATPase,** which transports H⁺ out of the cell and K⁺ into the cell with energy derived from cleavage of the high energy phosphate bonds of ATP. * Intercalated cells play a major role in renal regulation of the acid-base balance.

Question 129

principle cells

Answer 129

**K secretion** * They contain fewer mitochondria but extensive basolateral membrane, which contains Na⁺,K⁺-ATPase. * They are mainly located in the early part of the outer medullary collecting duct. * The high intracellular K⁺ generated by Na⁺,K⁺-ATPase coupled with the negative electrical potential in the tubular lumen favors the **passive movement of K⁺ out of the cell** into the tubular lumen. * Meanwhile, Na⁺ is efficiently reabsorbed in these cells. This process is tightly regulated by aldosterone

Question 130

Answer 130

principle cells in the collecting duct that **secrete K**

Question 131

in patients with decreased extracellular volume (hypovolemia, due to liquid loss because of bleeding, diarrhea, excessive vomiting), angiotensin II stimulates the function of ___ anti-porter leading to increase of ___ re-absorption and additional retaining of water to compensate the volume loss

Answer 131

Na⁺/H⁺ Na

Question 132

how does ANP effect collecting ducts?

Answer 132

atrial natriuretic peptide increase blood volume= stretch in atria= releases ANP **stimulates the release of Na with urine** by inhibiting Na channels

Question 133

antidiuretics will stimulate the production of ___ that allow water to leave urine

Answer 133

aquaporin

Question 134

\_\_\_ is a short peptide hormone that is produced and secreted by the cardiac atrial myocytes in response to stretch (high circulating blood volume). This hormone both increases GFR and inhibits Na⁺ re-absorption in the collecting ducts. The net result is an increase in Na⁺ and water excretion and decrease in circulating blood volume.

Answer 134

ANP (atrial natriuetic peptide)

Question 135

third factors increase the excretion of \_\_\_

Answer 135

sodium (similar to ANP atrial natriuretic peptide)

Question 136

\_\_\_ is a steroid mineralocorticoid hormone that is secreted by the adrenal cortex. Aldosterone acts to increase the body fluid volume and regulate the levels of K⁺.

Answer 136

aldosterone

Question 137

how does aldosterone work?

Answer 137

enters principle cell combines with R-aldo and enhances **sodium reabsorption** and **potassium secretion** through apical membrane channels and **chloride reabsorption** between the cells across the tight junction (zo).

Question 138

how is aldosterone triggered

Answer 138

low blood pressure (hypotension by angiotensin II) or by increased K in plasma (hyperkaliemia)

Question 139

what does aldosterone do to principle cells

Answer 139

* increasing the permeability of the apical membrane Na⁺ channels * increasing the numbers of Na⁺,K⁺-ATPases in the basolateral membrane and stimulating their activity * increasing apical K⁺ channels decreasing K⁺ back leak through basolateral K⁺ channels * increase in Na⁺ re-absorption – decrease in Na⁺ excretion – **increase in body fluid volume** * increase in K⁺ secretion – increase in K⁺ excretion - **decrease in extracellular K⁺ levels actions**

Question 140

what is the net results of aldosterone

Answer 140

* increase in Na⁺ re-absorption – decrease in Na⁺ excretion – **increase in body fluid volume** * increase in K⁺ secretion – increase in K⁺ excretion - **decrease in extracellular K⁺ levels actions**

Question 141

**History**. 1-year old spayed female Samoyed dog exhibits severe weakness, inappetence and vomiting since previous day. **Examination**. The dog looks lethargic, weak and markedly dehydrated. The heart rate is normal, but pulses are weak. No other abnormalities are found by physical examination. The urinalysis yields normal results with the urine specific gravity of 1.025. Abdominal X-rays are normal, but thoracic radiographs demonstrate a **small cardiac silhouette and small thoracic vessels**. The serum analysis: **creatinine - 2.5 mg/dL** (normal 0.6-1.2), **K⁺ - 6.5 mEq/L** (normal 3.6-5.6), **Na⁺ - 129 mEq/L** (normal 141-155), Cl^- - 97 mEq/L (normal 103-115). what is wrong?

Answer 141

**aldosterone not working** therefore there is high K, low Na and Cl and low blood volume

Question 142

•Cells ___ in fluids with decreased Na⁺ concentration or ___ when Na⁺ concentration is increased

Answer 142

swell shrink

Question 143

hyponatremia

Answer 143

too low Na+ cerebral edema

Question 144

what controls Na re-absorption in the proximal tubule

Answer 144

Question 145

how is Na reabsorbed in the loop of henle

Answer 145

Question 146

how is Na reabsorbed in the distal tubule

Answer 146

Question 147

how is sodium reabsorbed in the collecting tubules

Answer 147

Question 148

3 way to reabsorb Na

Answer 148

Question 149

Angiotensin II-aldosterone system – stimulate Na⁺ \_\_\_

Answer 149

**re-absorption**

Question 150

ANP and Third Factor(s) – inhibit Na⁺ \_\_\_

Answer 150

re-absorption

Question 151

To prevent a dangerous rise in the extracellular fluid K⁺ levels from the addition of K⁺ to the body, K⁺ can be shifted from ___ into the cells.

Answer 151

ECF

Question 152

Acidemia (pH\<7.4) release of\_\_\_ by cells into ECF

Answer 152

K⁺

Question 153

Alkalemia (pH\>7.4) increase in cellular uptake of __ from ECF

Answer 153

K⁺

Question 154

K in nephrons

Answer 154

90% is reabsorbed by proximal tubule and thick ascending limb of the loop of Henle K is then secreted back into urine by the distal tubules, cortical collecting ducts and the first part of the outer medullary collecting ducts.

Question 155

how is K reabsorbed ?

Answer 155

**in the proximal tubule**- passive by paracellular route by **solvent drag** However, in the late proximal tubule, some passive reabsorption of K⁺ may occur through K⁺-channels in the luminal and peritubular membranes. **in the thick ascending limb of the loop of henle-** paracellular **late distal tubule and collecting duct**- intercalated cells

Question 156

what part of the loop of henle is not involved in K reabsorption

Answer 156

thin segment of the loop of henle

Question 157

Answer 157

**_Thick ascending limb of the loop of Henle_** - The paracellular route is believed to be the primary mode of K⁺ reabsorption in the TAL. The presence of a K⁺ channel in the luminal membrane and a positive electrical potential in the lumen favor K⁺ reabsorption passively down its electrochemical gradient.

Question 158

in the late distal tubule and collecting duct what controls K

Answer 158

K⁺ secretion by principal cells K⁺ reabsorption by intercalated cells

Question 159

principle cells and K+ transport

Answer 159

K⁺ secretion by principal cells- Principal cells are located in the early part of the **outer medullary collecting duc**t. The high intracellular K⁺ concentration generated by Na⁺,K⁺-ATPase coupled with the negative electrical potential in the tubular lumen favors the passive movement of **K⁺ out of the cell into the tubular lumen**

Question 160

intercalated cell and K

Answer 160

K reabsorption •Intercalated cells in outer part of the **medullary collecting duc**t reabsorb K⁺ from the tubular fluid. K⁺ is actively transported into the cell from the lumen by a **H⁺,K⁺-ATPase**, which transports H⁺ out of the cell and K⁺ into the cell with energy derived from cleavage of the high energy phosphate bonds of ATP.

Question 161

hypokalemic polymyopathy in cats

Answer 161

**potassium decreased** * Can result from chronic renal failure * Approximately 20% of chronic renal failure cats are hypokalemic * Reason for particular susceptibility in cats are unknown * Characterized by a **generalized muscle weakness** (cats may even present with inability to hold up their head) * May be worsened by acidosis

Question 162

increased K intake will cause \_\_\_

Answer 162

increased quantity and activity of Na⁺,K⁺-ATPase pumps and amplification of principal cell basolateral membrane. **principal cells are in charge of K secretion**

Question 163

how does aldosterone effect K

Answer 163

Aldosterone enters the cells across the basolateral membrane and combines with its cytosolic receptor (R-Aldo), initiating a transcriptional program leading to a sequence of events that enhances **sodium reabsorption** and **potassium secretion** through apical membrane channels and chloride reabsorption between the cells across the tight junction (zo).

Question 164

Principal cells are located in the early part of the outer medullary collecting duct. The high intracellular K⁺ concentration generated by Na⁺,K⁺-ATPase coupled with the negative electrical potential in the tubular lumen favors the passive movement of K⁺ \_\_\_

Answer 164

out of the cell into the tubular lumen

Question 165

K⁺ ___ by the late distal tubule and collecting duct is increased with high Na⁺ intake

Answer 165

secretion

Question 166

how does H+ balance affect K

Answer 166

•K⁺ **secretion is reduced** by acute **increases in H⁺** (acute metabolic acidosis) and enhanced by acute decreases in H⁺ (acute metabolic alkalosis). Alkalosis or acidosis directly influence K⁺ uptake by stimulating or inhibiting, respectively, **Na⁺,K⁺-ATPase** in the late distal tubule and collecting duct. The number of K⁺ channels in the apical membrane also is increased. K⁺ secretion in acidosis and alkalosis is indirectly influenced by changes in tubular fluid flow rates and changes in Cl^- concentration.

Question 167

how does urine flow rate effect K

Answer 167

•The K⁺ concentration (chemical) gradient across the apical membrane is important in determining K⁺ secretion. **High urinary flow rate** past sites of K⁺ secretion prevents the buildup of K⁺ concentration in the tubular fluid, thus **favoring the secretion of K⁺.**

Question 168

how do drugs and toxins effect K?

Answer 168

•Diuretics are pharmacological agents, which alter the urinary excretion of water, Na⁺ and Cl^-, which, in turn, alters K⁺ excretion. Poisonous heavy metals (Hg, Cu, Ag, etc.) **inhibit Na⁺,K⁺-ATPase.**

Question 169

•Although only a small fraction of total body calcium, the plasma concentration of calcium is maintained within very narrow limits. However, only \_\_\_Ca²⁺ is under hormonal control.

Answer 169

ionized

Question 170

•Ca²⁺, Mg²⁺ and PO4 in plasma exist in two forms:

Answer 170

as free solutes in the complexes with plasma proteins Whereas free solutes are readily filtered in glomeruli, protein bound Ca²⁺, Mg²⁺ and PO4 _cannot_ undergo filtration.

Question 171

what type of calcium can undergo filtration by the kidney?

Answer 171

**free solutes** protein bound calcium can not fit through the filter

Question 172

how does Calcium, Mg and PO4 get reabsorbed?

Answer 172

* **Bulk reabsorption of Ca²⁺ and PO4 occurs in _the proximal tubule_:**•**60% of filtered Ca²⁺**•**20% of filtered Mg²⁺**•**70% of filtered PO4** * **active transport via Na⁺ – PO4 co-transporter** * **passive diffusion along chemical and electrochemical gradients** * **passive transport via solvent drag**

Question 173

what happens to Ca, Mg and PO4 in the loop of henle

Answer 173

* Basolateral membrane of the thick ascending limb of the loop of Henle contains Ca²⁺/Mg²⁺ sensors, which are implicated in the regulating the amount of Ca²⁺and Mg²⁺ reabsorbed here in response to the plasma levels of these cations. * Bulk reabsorption of Mg²⁺ occurs in the thick ascending limb of the loop of Henle. **Up to 60% of filtered Mg²⁺** is reabsorbed here, whereas this reabsorption accounts for a smaller fraction of Ca²⁺ (up to 20%) and a negligible fraction of PO4. * This reabsorption occurs predominantly via paracellular pathway.

Question 174

most of Mg is reabsorbed where?

Answer 174

ascending limb of the loop of henle (60%)

Question 175

•Ca²⁺and Mg²⁺ reabsorption in the \_\_\_of the loop of Henle parallels Na⁺ reabsorption since Ca²⁺and Mg²⁺ reabsorption in these segments occurs secondary to Na⁺ reabsorption.

Answer 175

thick ascending limb

Question 176

how to diuretics effect Ca in the thick ascending limb of the loop of Henle

Answer 176

* Loop diuretics such as furosemide **inhibit sodium chloride reabsorption** in the thick ascending limb of the loop of Henle by competing for the Cl site on the Na⁺-K⁺-2Cl^- cotransporter. * As a result, there will be a decrease in the lumen positive electrical gradient that drives passive Ca²⁺ transport and its reabsorption. * This ability to i**ncrease Ca²⁺ excretion** makes loop diuretics a key component of therapy for **hypercalcemia.**

Question 177

how to treat hypercalcemia

Answer 177

**give diuretic** blocks Cl-Na pump in the thick ascending limb of the loop of Henle this decreased gradient which prevents re-absorption of Mg and calcium

Question 178

what happens to Ca, Mg and PO4 in the distal nephron

Answer 178

•Small amounts of filtered **Mg²⁺ and PO4 are reabsorbed** in the distal convoluted tubule and cortical collecting duct. Almost all remaining Ca²⁺ is reabsorbed along the distal nephron. **Only 1-5% of filtered Ca²⁺ is found in the final urine.**

Question 179

•Approximately \_\_of filtered PO4 is excreted in the final urine

Answer 179

20%

Question 180

•Approximately ___ of filtered Mg²⁺ is excreted in the final urine

Answer 180

10%

Question 181

\_\_\_ is the major regulator of renal excretion of Ca²⁺, Mg²⁺ and PO4.

Answer 181

•Parathyroid hormone (**PTH**)

Question 182

PTH is released when

Answer 182

* decreased plasma concentrations of Ca²⁺ * decreased plasma concentrations of Mg²⁺ (up to ~0.8 mg/100 ml)

Question 183

what does PTH inhibits what and stimulates what?

Answer 183

Inhibition of PO4 reabsorption in the proximal tubule 2. Stimulation of **reabsorption** of Ca²⁺and Mg²⁺ in thick ascending limb of the loop of Henle. Stimulation of **reabsorption** of Ca²⁺ in the collecting ducts **The net effect of PTH is restoration in plasma levels of Ca²⁺and Mg²⁺**

Question 184

the net effect of PTH is the \_\_

Answer 184

return of Ca and Mg plasma levels to normal. low calcium will trigger PTH to cause reabsorption of Ca and Mg in the thick ascending limb of the loop of henle and reabsorption of Ca in the collecting duct. it will also inhibit the reabsorption of PO4 in the proximal tubule

Question 185

regulation of renal excretion of Ca, Mg and Po4 is by

Answer 185

PTH

Question 186

•PTH also stimulate the enzymatic conversion of vitamin D to the active form ^1,25-(OH)2D3 (a.k.a. \_\_\_) via activation of 1-hydroxylase that catalizes final hydroxylation of vitamin D.

Answer 186

_calcitriol_

Question 187

Calcitriol does what?

Answer 187

• stimulate **intestinal absorption of calcium and phosphate** increase **renal tubular Ca reabsorption** by the distal tubule. •These functions allow vitamin D to achieve the primary function of enhancing the availability of calcium and phosphate required for new bone formation and prevention of hypocalcemia and hypophosphatemia.

Question 188

calcium reabsorption in the distal tubule

Answer 188

The distal tubule and adjacent segments are the major sites of regulation of urinary excretion of Ca²⁺ under the influence of PTH and calcitriol. Ca²⁺ can enter the cell along the electrochemical gradient (formed by Na⁺ movements) through apical Ca²⁺ channels and calcitriol-dependent Ca-binding protein. Extrusion of Ca²⁺ across the basolateral membrane occurs via 3Na⁺-1Ca²⁺ exchanger and Ca ATPase pump

Question 189

•The osmolality of body fluids is maintained constant at ___ mosmoles/kg water.

Answer 189

~285

Question 190

•Water excretion in kidney is tightly regulated. Urine osmolality can range from 60 mosmoles (\_\_\_ urine, the body is in a state of positive water balance) to 1200 mosmoles (\_\_\_ urine, the body is in a state of negative water balance).

Answer 190

dilute concentrated

Question 191

Concentration and dilution of the urine leads to alterations in blood volume and, consequently, to changes in ___ function, blood pressure and perfusion of tissue

Answer 191

cardiac

Question 192

•When the renal excretion of water is increased and the urine flow is greater than normal (\> 1 ml/min in an adult human).

Answer 192

diuresis

Question 193

Diuresis caused by the presence of extra, non-reabsorbed solute in the tubular lumen (e.g., diabetes mellitus).

Answer 193

osmotic diuresis

Question 194

Diuresis caused by a decrease in water reabsorbed from the tubule lumen (e.g., diabetes insipidus).

Answer 194

water diuresis

Question 195

When the renal excretion of water is decreased and the urine flow is less than normal (\< 1 ml/min in an adult human).

Answer 195

***_Antidiuresis_***

Question 196

Urine with an osmolality less than that of plasma (\< 300 mosm).

Answer 196

hypoosmotic

Question 197

Urine with an osmolality greater than that of plasma (\> 300 mosm).

Answer 197

hyperosmotic

Question 198

**•\_\_\_** **is responsible for the reabsorption of the bulk of filtered solutes.**

Answer 198

**The proximal tubule**

Question 199

•In proximal tubule, solutes and water are reabsorbed \_\_\_~60-70% of the ultrafiltrate is reabsorbed in this part of nephron.

Answer 199

isotonically.

Question 200

•Water follows actively transported solutes (\_\_\_) as well as solutes moving along their gradients (amino acids, K⁺, Cl^-, etc.) and moves from the luminal fluid into the interstitial fluid

Answer 200

Na⁺

Question 201

two ways water is reabsorbed in the proximal tubule

Answer 201

1. through the cells forming the proximal tubule (**transcellular pathway)** 2. **via solvent drag** through the zonae occludae - contacts between these cells (paracellular pathway).

Question 202

•Water further moves from the interstitial fluid to the bloodstream of peritubular capillaries because of high ___ pressure of blood plasma (\_\_\_ forces) and low hydrostatic pressure within capillaries.

Answer 202

oncotic Starling’s

Question 203

two types of nephrons

Answer 203

* 1. cortical (with short loop of Henly) - B * 2. medullar (with long loop of Henle) - A

Question 204

would camels have short or long loops of henle

Answer 204

long to get as much water back as possible

Question 205

•Concentration or dilution of urine is **not** a result of **active** reabsorption or secretion of water. In the renal tubule, the movement of water to areas of high osmolality allows for its \_\_\_reabsorption.

Answer 205

_passive_

Question 206

_The three components of the urinary concentrating system are:_ * 1. Countercurrent multiplier system of the \_\_\_. * 2. Countercurrent exchange system of the \_\_\_\_. * 3. ____ and its effects on the permeability of the distal tubule and the collecting duct.

Answer 206

loop of Henle vasa recta Antidiuretic hormone (ADH)

Question 207

what part of the loop of henle is permeable to water

Answer 207

descending loop

Question 208

what part of the loop of henle is permeable to Na

Answer 208

ascending thin and thick and distal water can not leave these sections unless aquaporin is added

Question 209

explain countercurrent multiplier

Answer 209

•_Significant differences in the properties of the two limbs of the loop of Henle_ contribute to the generation of an osmotic gradient in the interstitial tissue of the kidney that increases in magnitude from the cortex to the renal papilla.

Question 210

•_Significant differences in the properties of the two limbs of the loop of Henle_ contribute to the generation of an ___ gradient in the interstitial tissue of the kidney that increases in magnitude from the cortex to the renal papilla.

Answer 210

osmotic

Question 211

The ___ is permeable to water but not NaCl. Water goes to the interstitial tissue, urine concentrates _b._ The ___ limb is permeable to NaCl but not water. NaCl goes to the interstitial tissue, urine dilutes. _c._ The ____ limb actively pumps NaCl out of the tubule fluid and into the interstitium. **Net result: formation of osmotic gradient**

Answer 211

thin descending limb (TDL) thin ascending thick ascending (TAL - impermeable to water)

Question 212

why does osmolarity increase from 300 to 1200 in the thin descending loop of henle

Answer 212

the concentration of Na outside of the loop and the inability of Na to leave the descending loop causes water to leave the descending loop to try to make the osmolarity even

Question 213

In mammals (but not in birds), ___ - an end product of protein catabolism - also constitutes a significant portion of the corticomedullary interstitial osmotic gradient.

Answer 213

urea Most urea is passively reabsorbed by the proximal tubule, but during antidiuresis, urea is reabsorbed by the collecting duct, as well.

Question 214

The selective reabsorption of NaCl without water in the TAL results in a ___ interstitium.

Answer 214

hypertonic

Question 215

The capillary system that perfuses the medullary region of the kidney is termed the \_\_\_

Answer 215

**vasa recta**

Question 216

The vasa recta are specialized peritubular capillaries, which function in \_\_\_exchange

Answer 216

countercurrent

Question 217

the ___ are responsible for returning the water reabsorbed by the late distal tubules and collecting ducts to the systemic vasculature.

Answer 217

vasa recta

Question 218

. Since the vasa recta enter and exit the renal tissue at the\_\_\_ the gradient is not washed out.

Answer 218

cortex

Question 219

Answer 219

vasa recta blood moving- things more likely to come in then leave when presented with a gradient starting at 300, more likely for NaCl to come in increasing gradient, when it turns H20 more likely to come in to decrease gradient- ends at 300

Question 220

The presence or absence of ___ (a.k.a. antidiuretic hormone, _ADH_) determines whether the urine is concentrated or dilute.

Answer 220

_vasopressin_

Question 221

ADH is a small 9 amino acid-containing ___ hormone produced in the supraoptic nuclei near the pituitary gland in the brain.

Answer 221

peptide

Question 222

ADH is stored and released from neurons in the\_\_\_pituitary gland.

Answer 222

posterior

Question 223

\_\_\_regulates permeability of collecting ducts to water

Answer 223

ADH

Question 224

If ADH is absent, the distal tubule and collecting duct are __ to water, preventing water movement out of the tubule into the hypertonic interstitium

Answer 224

impermeable

Question 225

what happens in ADH present in collecting duct

Answer 225

ADH allows water to diffuse out into the interstitium will concentrate urine

Question 226

how does ADH let water out

Answer 226

inserts aquaporines into the membrane of the collecting duct

Question 227

ADH and urea

Answer 227

ADH results in insertion of urea channels Thus, during antidiuresis urea constitutes a greater portion (as much as 40%) of the corticomedullary gradient than during diuresis (10%).

Question 228

proper water balance is based on what two elements?

Answer 228

1. water output (regulated in part by ADH) 2. water input (regulated through the sensation of thirst and the behavioral response to this sensation)

Question 229

baroreceptors in the left atrium, carotid sinus and aortic arch monitor \_\_\_

Answer 229

arterial pressure: too low will increase ADH to conserve water, too high will decrease ADH to get rid of water

Question 230

Changes in plasma osmolality are monitored by ___ near the hypothalamus

Answer 230

osmoreceptors

Question 231

When plasma volume \_\_\_and/or plasma osmolality \_\_\_, inhibition is relieved and ADH is released into the blood.

Answer 231

decreases increases,

Question 232

Changes in plasma osmolality as small as __ will trigger increases or decreases in plasma ADH.

Answer 232

1%

Question 233

how far does plasma volume drop to stimulate ADH release

Answer 233

10%

Question 234

When plasma volume and/or arterial pressure decreases and/or plasma osmolality increases, an increase in ___ intensity occurs

Answer 234

thirst

Question 235

why do horses not drink after exercise

Answer 235

lose hypertonic sweat lose more Na then water need electrolyte supplement

Question 236

urine more concentrated than glomerular filtrate

Answer 236

Hypersthenuria

Question 237

•urine more dilute than glomerular filtrate

Answer 237

Hyposthenuria

Question 238

water deprivation test

Answer 238

assessing ability of tubules to conserve water with stimulus of serum osmolality rule out **diabetes insipidus(dont produce ADH)** for PU/PD * The bladder is emptied, and water and food are withheld (usually 3-8 hr) to provide a maximum stimulus for ADH secretion. The animal should be monitored carefully to prevent a loss of \>5% body wt and severe dehydration. * Urine and plasma osmolality (or USG) should be determined. At the end of the test, urine specific gravity is **\>1.025** in those animals with only a **partial ADH** deficiency or with antagonism to ADH action caused by hypercortisolism. There is **little change** in specific gravity in those animals with a **complete lack of ADH** activity, whether due to a primary loss of ADH or to unresponsiveness of the kidneys .•A response to injected ADH (modified deprivation test) is often used to corroborate the diagnosis. •Do NOT perform water deprivation test in animals that are azotemic or dehydrated yet did not concentrate their urine – these animals have already failed this test

Question 239

The dog is alert and active. Urinalysis is normal except for urine specific gravity is **1.002** (osmolality 152mOsm/kg). The dog is admitted for a water deprivation test, however, the urine **fails to concentrate** despite a 5% loss in body weight. Administration of vasopressin followed by urinalysis an hour later reveal urine with specific gravity of 1.029 and osmolality 852mOsm/kg.

Answer 239

diabetes insipidis (does not produce ADH) can't concentrate urine

Question 240

pu/pd increased glucose decrease pH, increase CO2, low bicarbonate

Answer 240

diabetes acidosis

Question 241

exercise intolerance, crackles ph 7.37 PO2 low PCO2 high

Answer 241

pneumonia respiratory acidosis

Question 242

two ways to get rid of acid

Answer 242

H converted to CO2 and H20 and exhales kidney removes H and HCO in urine

Question 243

The most abundant buffers in the body fluids are 1. bicarbonate/CO₂ in the \_\_\_(400 mEq), 2. bicarbonate in the ___ (400 mEq) 3. \_\_\_groups of intracellular proteins (~ 400 mEq) 4. intra and extracellular ___ (40 mEq).

Answer 243

ECF ICF and bone histidine phosphates

Question 244

buffers contribute into pH maintenance within the limits that are compatible with life (pH 6.8-7.8), therefore, according to the \_\_\_principle

Answer 244

isohydric ## Footnote pH = pK₁ + log ([HCO₃^-]/[H₂CO₃]). **base/acid** pH = pK₂ + log ([protein^-]/[Hprotein]) pH = pK₃ + log ([HPO₄^2-]/[H₂PO₄^-])

Question 245

bicarb/CO2

Answer 245

CO2 + H2O \<=\> H2CO3 \<=\> H⁺ + HCO3^- volatile acid

Question 246

the carbonic H₂CO₃-HCO₃^- system is in equilibrium with a gas (CO₂), CO₂ is called a \_\_\_acid

Answer 246

volatile

Question 247

how does kidney regulate HCO3: * conserving or excreting the HCO₃^- present in the glomerular \_\_\_ * producing new HCO₃^- which enters the body fluids as the kidneys excrete ammonium salts and titratable acids (this sum is called \_\_\_) in the urine

Answer 247

ultrafiltrate net acid

Question 248

If urine pH \< 6, the concentration of HCO₃^- in the urine is

Answer 248

very low (e.g.\< 0.1 mEq/L). The glomerular ultrafiltrate has 24 mM. Thus, most HCO₃- filtered (4500 mEq/day) is reabsorbed, mostly (90%) along the proximal tubules and also in collecting ducts

Question 249

The kidneys can generate (produce) new HCO3^- through: * urinary excretion of ____ salts * urinary excretion of \_\_\_

Answer 249

**ammonium (NH₄⁺)** **titratable acids.**

Question 250

normal HCO3 in the blood

Answer 250

24mM

Question 251

how much bicarb is kicked out of the cell into the interstitial fluid with every mole of Na moved out by the Na/K pump

Answer 251

3 moles of bicarb for every 1 mole of Na this loss of bicarb in the cell will cause more formation of bicarb in the cell the H⁺ are moved out of cell by Na/H antiporter into the urine in the urine H will bind with bicarb to form CO2 and H20

Question 252

how is bicarb preserved in the kidney

Answer 252

3 moles of bicarb for every 1 mole of Na this loss of bicarb in the cell will cause more formation of bicarb in the cell the H⁺ are moved out of cell by Na/H antiporter into the urine in the urine H will bind with bicarb to form CO2 and H20 * Hydration reaction, CO₂ + H₂O \<=\> H₂CO₃ \<=\> H⁺ + HCO3^- occurs in the cytoplasm of the tubular epithelial cell (catalyzed by soluble intracellular Type II carbonic anhydrase). * CO₂ in the extracellular fluid freely diffuses into the cells, promoting more hydration * After hydration, the H⁺ formed is secreted into the tubular lumen (in exchange for Na⁺, where it combines with the bicarbonate tubular buffer to form H₂CO₃ * Tubular H₂CO₃ de-composes into H₂0 and CO₂ (catalyzed by the brush border carbonic anhydrase). Tubular H₂0 and CO₂ are excreted with urine. * The intracellular HCO3^- formed from hydration diffuses into the extracellular fluid through the basolateral membrane in a 3:1 co-transport with Na⁺ exchanged for H⁺. *The net result is that NaHCO₃ disappears from the lumen and appears in the blood-side of the proximal tubule cells.*

Question 253

proximal tubule reabsorption of bicarb results is that ___ disappears from the lumen and appears in the blood-side of the proximal tubule cells.

Answer 253

*NaHCO₃*

Question 254

what change in pH will cause an increase reabsorption of HCO3 in the proximal tubule

Answer 254

**decreases in cell pH** (due to metabolic acidosis, respiratory acidosis or to decreases in cell K⁺) via acute activation of Na⁺-H⁺ exchange and chronic induction of Na⁺-3HCO3^- co-transporters, and

Question 255

**high levels of** \_\_\_stimulate Na⁺-H⁺ exchange to promote reabsorption of bicarb in the proximal tubule

Answer 255

**angiotensin II**

Question 256

urinary excretion of ammonium

Answer 256

Question 257

In \_\_\_, increases in renal NH₄⁺ excretion are due to re-routing of NH₃ from renal venous blood to the urine due to a more acidic urine pH and sometimes, to increases in urine flow. In addition, an acid intracellular pH activates mitochondrial glutamine transport and metabolism (deamidation ) and oxidation of the resulting a-ketoglutarate.

Answer 257

**acute** **acidosis**

Question 258

In , \_\_\_here is also induction of basolateral and mitochondrial glutamine transporters, of glutaminase, and other enzymes that participate in the oxidation of glutamine. These adaptations to chronic acidosis allow large amounts of ammonium to be excreted at any urine pH, even at pH 7.

Answer 258

**chronic metabolic acidosis**

Question 259

excretion of titratable acid

Answer 259

Question 260

•The major buffer in urine is \_\_\_. At pH 7.4 as in the glomerular filtrate, only 20% of the phosphate is in the \_\_\_phosphate form (H₂P0₄^-) and 80% is in the ___ form (HPO₄^2-).

Answer 260

phosphate di-acid monoacid

Question 261

•For every proton secreted that titrates the phosphate in the lumen, there is generation of one molecule of ___ that enters the circulation and helps restore the buffering capacity of the body

Answer 261

bicarbonate

Question 262

\_\_protonated phosphates are excreted.

Answer 262

•Di (H₂PO₄^-)

Question 263

The rate of urinary excretion of TA depends on: * the *urine pH* * *efficiency of ___ antiporter* * the *rate of excretion of buffers* (\_\_\_, creatinine and b -hydroxyburyrate).

Answer 263

*Na⁺/H⁺* phosphate

Question 264

In acidosis, TA excretion is enhanced due mostly to the low urine pH and to a small increase in phosphate excretion (due to reduced reabsorption and loss of \_\_\_\_).

Answer 264

bone phosphate 10 fold increment (from 30 to 300 mmol/day) of TA excretion observed in severe ketoacidosis (diabetis) when the urine pH reaches values as low as 4.5.

Question 265

The sum of the NH₄⁺ excretion and the TA excreted (in mEq) minus the bicarbonate (mEq) that might escape in the urine is called ____ and equals the milliequivalents of new bicarbonate produced (generated) by the kidneys to restore the buffer reserves of the body fluids.

Answer 265

NET ACID EXCRETION

Question 266

H secretion in the proximal tubule

Answer 266

* Within dotted line – H⁺/HCO3^- cycle between cell and the tubular lumen – using activities of intra- and extra-cellular carbonic anhydrases and following the principles of renal reabsorption of bicarbonate * Secretion primarily occurs via a Na⁺-H⁺ exchanger (which also can function as a Na⁺/NH₄⁺ co-transporter) * Ammonium (generated from metabolism of glutamine) can be secreted as NH₄⁺ * In addition, NH₃ can diffuse into the tubular lumen, where it can be protonated in the distal nephron * Secretion primarily occurs via an active H⁺ ATPase pump in the apical membrane and, secondarily, in an exchange with K⁺ via the NHE-3 proton/potassium ATPase) * Secreted protons combine with NH₃ , which comes from proximal tubule or can diffuse transcellularly from the interstitium * In addition, secreted protons also buffered by filtered HPO₄^2- to form H₂PO₄^-

Question 267

•Secretion of H primarily occurs via an active \_\_\_ATPase pump in the apical membrane and, secondarily, in an exchange with K⁺ via the NHE-3 proton/potassium ATPase)

Answer 267

H⁺ out pump and K in H out pump

Question 268

When pH_a (arterial blood pH) differs from 7.4 +/- 0.02 (or the [H⁺] differs from 40 +/- 2 nEq/L) there occurs ____ (pH_a \< 7.38, [H⁺] \> 42 nEq/L) or \_\_\_(pH_a \> 7.42, [H⁺] \< 38 nEq/L).

Answer 268

* acidemia* * alkalemia*

Question 269

When the pH_a change is due primarily to a change in [HCO₃^-] from its normal value of 24 mM, there is \_\_\_([HCO₃^-] \< 22 mM) or \_\_\_\_([HCO₃^-] \> 26 mM).

Answer 269

* metabolic acidosis* * metabolic alkalosis*

Question 270

***acidosis*** **and** ***alkalosis*** **refer to ___ that lead to pH changes in blood**

Answer 270

**physiologic processes**

Question 271

normal amount of PaCO2 normal amount of HCO3 normal blood pH

Answer 271

PaCO2=40 HCO3= 24 mM pH= 7.4

Question 272

will K increase or decrease will acidosis?

Answer 272

increase (hyperkalemia) H will be pulled into cells and K and Na will be pushed out

Question 273

will k increase or decrease with alkalosis?

Answer 273

decrease cell will kick out H and pull in K and Na leading to hypokalemia

Question 274

what is the pH and HCO3 during acidosis

Answer 274

pH, 7.38 bicarb \< 22

Question 275

what causes metabolic acidosis

Answer 275

* Extrarenal loss of bicarbonate, with hyperchloremia and increased urinary excretion of NH₄⁺ (diarrhea (scours) of newborn calves) * Urinary loss of HCO₃^- (alkaline urine, with high bicarbonate, and little NH₄⁺) – some diuretics * Accumulation of organic anions (diabetis and other disorders leading to lactacidosis and/or ketoacidosis). Lactacidosis can develop in minutes (as in shock) or longer (lactating cows\*). * Decreased kidney production of HCO₃^- (hyperchloremia) and low urinary excretion of ammonium; severe chronic renal failure may result in metabolic acidosis and low urinary NH₄⁺ excretion.

Question 276

how to compensate for metabolic acidiosis

Answer 276

**•****Immediate buffering** by reaction with ECF HCO₃^- represents 42% of rapid (~2 hrs) buffering of acid. HCl + NaHCO₃ =\> NaCl+ H₂CO₃ + CO₂ + H₂0 **•****Respiratory compensation**. A low pH_a stimulates lung ventilation (V_A), so P_aCO2 decreases minimizing the decrease in pH_a. For each 1 mM decrease in [HCO₃^-] a 1 mm Hg drop in P_aCO2 is expected. **•****Tissue phase.** Entry of H⁺ into cells accounts for 57% of rapid (~2 h) buffering of poorly permeable acids (HCl or H₂SO₄). This phase is capable of buffering 100% of the acid by 24 h, and is due to the ion exchanges **•****Renal phase.** Generation of bicarbonate through urinary excretion of ammonium and titratable acids, restores the depleted cell HCO₃^- and buffer base reserves over 2-3 days.

Question 277

pH and bicarb for alkalosis?

Answer 277

pH \>7.42 bicarb \>26

Question 278

causes of metabolic alkalosis

Answer 278

* Loss of gastric juice by vomiting or prolonged gastric lavage. * Side effect of diuretics and other forms of ECF volume contraction .•Hyperaldosteronism : **volume depletion promotes renal H⁺ secretion,** generation and retention of HCO₃^-. •In hypokalemia, K⁺ shifts out of cells in exchange for H⁺, inducing extracellular alkalosis and intracellular acidosis.

Question 279

Hypovolemia-triggered production of ___ leads to the stimulation of the anti-porter that facilitates the exchange of intracellular protons with lumenal Na⁺ in the proximal tubule. That leads to increased secretion of H⁺ and, accordingly, alkalosis.

Answer 279

Angiotensin II

Question 280

how to compensate for metabolic alkalosis

Answer 280

Compensations **•****Respiratory**. As pH_a increases, V_A is depressed and P_aCO2 increases (P_aCO2 \> 42 mm Hg). This normalizes blood pH but is limited by ensuing hypoxia. For each 1 mM rise in HCO₃^- there is expected a 0.7 mm Hg rise in P_aCO2. **•****Cell ionic exchanges**. Some 25% of the bicarbonate load is neutralized by H⁺ derived from intracellular buffers that exchange the H⁺ for extracellular Na⁺. In addition, ~2% of extracellular HCO₃^- enters red cells in exchange for Cl^-. **•****Metabolic.** High pH_a increases production of lactic and citric acids which decrease [HCO₃^-]. Increases in endogenous organic acid neutralize ~5 % of an acute HCO₃^- load. **•****Renal excretion** of HCO₃^- rises when its concentration in plasma increases. Lowering of [HCO₃^-]_pl is limited by high renal reabsorption rate stimulated by high P_aCO2, by ECF volume contraction, by hyperaldosteronism, by K⁺ depletion, and by hypochloremia. b-intercalated cells in collecting ducts secrete bicarbonate, increasing its urinary excretion.

Question 281

causes of respiratory acidosis

Answer 281

Alveolar hypoventilation (airway obstruction (bronchitis, asthma), neuromuscular disorders, diseases of central nervous system)

Question 282

compensation for respiratory acidosis

Answer 282

Compensations •**Fast cell ion exchanges**. An acute rise in [HCO₃^-]_pl is due to exchange of ECF H⁺ for ICF Na⁺ or K⁺ and to exchange of ECF Cl^- for ICF HCO₃^-. These rapid exchanges are associated with CO₂ buffering by intracellular proteins. **•****Metabolic.** Reduced production of lactic acid contributes about 5% to the acute increase in [HCO₃^-]_pl. **•****Renal.** Increased HCO₃^- reabsorption stimulated by high P_aCO2 prevents urinary loss of bicarbonate. In the chronic stage, enhanced renal NH₄⁺, and TA excretion contribute to further increase [HCO₃^-] in ECF and ICF above normal, returning pH towards normal. As the pH stimulus decreases, renal NH₄⁺ and titratable acid excretion subside. Renal reabsorption of bicarbonate is elevated as long as the P_aCO2 is high.

Question 283

causes of respiratory alkalosis

Answer 283

Alveolar hyperventilation (prolonged fever, high altitude, controlled artificial ventilation during general anesthesia, anxiety/hysteria, salycilates (aspirin, etc.) excess) )

Question 284

compensation for respiratory alkalosis

Answer 284

Compensations •**Cell buffers (acute)**. A decrease in [HCO₃^-] for decrease in P_aCO2 - due to enhanced dissociation of H⁺ from cell buffers. Cell H⁺ exchange for ECF Na⁺ and K⁺ and react with the ECF HCO₃^-, reducing its concentration. Extracellular HCO₃^- enters cells in exchange for Cl^-. **•****Renal (in the _chronic_ state) -** due to increased HCO₃^- excretion associated with the low P_aCO2, which decreases HCO₃^- reabsorption. Urinary excretion of NH₄⁺ and TA are transiently reduced, leading to accumulation of metabolic and dietary acids, which help reduce ECF [HCO₃^-]. Eventually urinary HCO₃^- excretion ceases and excretion of NH4⁺ and TA resumes. **•****Metabolic (in the _chronic_ state) -** by increased production of lactic and citric acid that react with and reduce [HCO₃^-]_ecf.