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22 spring: Physiology > exam 2 lecture 23-28 > Flashcards

exam 2 lecture 23-28 Flashcards

1
Q

functions of kidney

A
  • 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
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2
Q

four homeostatic functions of the kidney

A
  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
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3
Q

what are 3 endocrine functions of the kidney

A

•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
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4
Q

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

A

Erythropoietin

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5
Q

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

A

calcitriol

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6
Q

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

A

Renin, bradykinins and prostaglandins

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7
Q

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

A

proteolysis

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8
Q

filtration occurs where in the kidney?

A

cortex

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9
Q

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

A

medulla

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10
Q

bladder expels urine from the body by ___

A

micturition

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11
Q

the two functions of the tubule of the nephron are?

A

reabsorption (from tubule back into the blood)

secretion (from blood into nephron)

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12
Q

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.

A

glomerular

peritubular

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13
Q

Juxtaglomerular apparatus

A

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

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14
Q

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

A

macula densa

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15
Q

flow of blood in the kidney

A

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

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16
Q

red blood cell cast

A

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

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17
Q

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

A

proteins

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18
Q

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

A

protein

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19
Q

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

A

glomerular capillary bed

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20
Q

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

A

arterial pressure

(kidney close to aorta= high blood pressure)

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21
Q

structure of glomerular capillary wall

A
  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)
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22
Q

whole in the capillary endothelium to allow small molecules through

A

fenestrae

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23
Q

glomerular basement membrane is made of 3 layers of ___

A

glycoproteins

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24
Q

what are the three layers of the glomerular basement membrane?

A

lamina rara externa

interna

lamina densa

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25
Q

visceral endothelium of the glomerular capillary wall are made of ___

A

podocytes

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26
Q

___ hold podocytes together

A

slit diaphragm

(proteins)

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27
Q

what is the opposing force for in the glomerulus?

A

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)

PBS hydrostatic pressure: from the bowman’s space (very small)

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28
Q

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

A

PGC

hydrostatic pressure in the glomerular capillary

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29
Q

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

A

afferent

efferent

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30
Q

PGC is the primary target of regulatory mechanisms that control ___

A

GFR

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31
Q

∏GC

A

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 PGC. Meanwhile, most of the plasma proteins are retained in the capillary lumen. Therefore, the plasma oncotic pressure (∏GC) increases significantly along the capillary bed.
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32
Q

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

A

plasma oncotic pressure

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33
Q

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

A

increases

fluid leaves, proteins stay

therefore the pressure of protein to not protein increases

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34
Q

what can cause hydrostatic pressure in the bowman’s space (PBS) to increase?

A

obstruction- nephrolithiasis, tumors, etc

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35
Q

•___ - “sieve” function –– contributes to the co-efficient of ultrafiltration (Kf) along with filtration surface

A

Permeability

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36
Q

what things can freely filter out of glomerulus

A

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

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37
Q

what things are poorly filtered by the glomerulus?

A

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

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38
Q

what factors affect permeability of polypeptides through the glomerulus?

A
  • 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

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39
Q

cations or anions can filter more easily?

A

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

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40
Q

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

A

glomerulonephritis

happens during proteinuria

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41
Q

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

A

cation (positive) easiest

neutral

anions (negative) hardest

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42
Q

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

A

GFR

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43
Q

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

A

Systemic factors (renal modulation of systemic blood pressure and intravascular volume)

Intrinsic factors (control of renal blood flow, PGC, and Kf)

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44
Q

GFR is maintained by intrinsic factors such as __

A

control of renal blood flow, PGC and Kf

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45
Q

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

A

extraglomerular mesangial cells

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46
Q

extraglomerular mesangial cells (Juxtaglomerular cells) trigger ___ system

A

renin-angiotensin-aldosteron system

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47
Q

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

A

renin

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48
Q

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

A

decrease

hypotension

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49
Q

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

A

angiotensinogen

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50
Q

•Angiotensin I is further converted to angiotensin II by ___

A

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

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51
Q

how does angiotensin II work

A
  • 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.
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52
Q

renin pathway

A

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

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53
Q

angiotensin II triggers the release of this mineralocorticoid steroid hormone ___from the adrenal gland

A

aldosterone

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54
Q

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

A

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

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55
Q

what does angiotensin II do to renal afferent arterioles?

A

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

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56
Q

constriction of the afferent arteriole does what to pressures?

A

increases renal vascular resistance (thereby reducing RPF) and decreases the intraglomerular pressure and GFR

decreases PGC, GFR and RPF (renal plasma flow)

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57
Q

constriction of the efferent arteriole does what to pressures?

A

increases PGC and GFR

decreases Renal plasma flow

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58
Q

prolonged increased blood pressure will do what to kidneys?

A

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

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59
Q

enalapril is a ___

A

ace inhibitor

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

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60
Q

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 ___

A

acute renal failure.

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61
Q

two intrinsic factors regulating GFR

A
  • The myogenic reflex
  • The tubulo-glomerular feedback.
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62
Q

myogenic reflex

A
  • 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.

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63
Q

tubulo-glomerular feedback

A

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 PGC 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.
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64
Q

how to measure GFR

A

•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
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65
Q

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

A

plasma concentration

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66
Q

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 ___

A

re-absorption.

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67
Q

what is an indicator substance of choice to measure GFR?

A

inulin (a xenobiotic)

•Inulin is freely filtered by the glomerulus but is neither absorbed nor secreted by the renal tubular cells.

•GFR = Cinulin = (Uinulin x V)/Pinulin

  • where GFR, as well as Cinulin is in ml/min
  • Uinulin – 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
  • Pinulin – the mean plasma inulin concentration during time T
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68
Q

calculate GFR if

P=1 mg/ml

U= 100 mg/ml

V= 1.25 ml/min

A

GFR= (U x V)/P

(100 x 1.25)/1

125 ml/min

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69
Q

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

A

creatinine

(can not be used for birds)

(very good for dogs, some reabsorption for cats)

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70
Q

•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

A

GFR

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71
Q

why is creatinine clearance slightly overestimated in humans and felines

A

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

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72
Q
A

GFR roughly = to % nephrons working

creatine above 1.2 = kidney not working well

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73
Q

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 ___

A

renal plasma flow

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74
Q

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

A

filtration fraction (FF)

FF= GFR/RPF

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75
Q

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

A

fractional excretion (FE)

•FEX = (UX x V) / (PX x GFR)

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76
Q

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

A

fractional excretion (FE)

  • FEX = (UX x V) / (PX 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
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77
Q

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

A

> 1

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78
Q

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

A

< 1

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79
Q

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.

A

PUPD
polyuria and polydipsia

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80
Q

serum creatinine level is 8.7 mg/dL (normal 0.5-1.2)

this is called ___

A

azotemia

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

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81
Q

uremia

A

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

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82
Q

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)

A

something is eating membrane of glomerulus and allowing proteins and RBC into the nephrons

proteinuria

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83
Q

proteinuria

A
  • 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)

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84
Q

____ refers to disorders in which there is increased glomerular permeability to macromolecules

A

Nephrotic syndrome

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85
Q

Nephrotic syndrome

A

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

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86
Q

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

A

reabsorption

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87
Q

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

A

secretion.

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88
Q

what three things are re-absorbed 100%

A

glucose

polypeptides

potassium

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89
Q

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

A

FER (fractional excretion rate)

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90
Q

•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)

A

urinary concentration (U)

For the substance X : FERx = (Ux/Px)/(Ucreatinine/Pcreatinine) x 100%

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91
Q

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

A

FAR fractional re-absorption rate

•FAR = 100% - FER

For the substance X : FERx = (Ux/Px)/(Ucreatinine/Pcreatinine) x 100%

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92
Q

how to calculate FAR

A

For the substance X : FERx = (Ux/Px)/(Ucreatinine/Pcreatinine) x 100%

•FAR = 100% - FER

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93
Q

where does most re-absorption take place?

A

proximal tubule

(large brush border = increased surface area)

the trans-cellular pathway, and the paracellular pathway.

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94
Q

how does the proximal tubule move fluid

A

the trans-cellular pathway

the paracellular pathway.

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95
Q

the trans-cellular pathway of the proximal tubule

A

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)
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96
Q

substances reabsorbed in the proximal tubule go where?

A

peritubular plexus

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97
Q

para cellular pathway in the proximal tubule

A

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

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98
Q

•Paracellular transport occurs by passive diffusion (along concentration gradient) or by ___

A

solvent drag

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

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99
Q

starling forces

A

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.

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100
Q

3 ways to reabsorb in the proximal tubule

A
  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+.

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101
Q

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

A

Na+.

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102
Q

solvent drag in the proximal tubule works for __

A

reabsorption of K+ and Cl-

Cl- also moves by passive diffusion

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103
Q

passive diffusion in the proximal tubule is for ___

A

calcium, magnesiuma and Cl-

(Cl- also moves by solvent drag)

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104
Q

active transport in the proximal tubule is for

A

reabsorption of Na+

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105
Q

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

A

electro-chemical gradients

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106
Q

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

A

phosphate,

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107
Q

Na- K ATPase pump

A

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.

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108
Q

what happens to K after Na/K pump

A

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

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109
Q

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

A

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.

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110
Q

movement of Na+ causes Cl- to do what?

A

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.

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111
Q

transport maximum

A

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)

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112
Q

how do peptides get reabsorbed in the proximal tubule?

A

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

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113
Q

how do hormones get reabsorbed in the proximal tubule?

A

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.

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114
Q

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

A

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
115
Q

tubular secretion is by ___

A

passive or active secretion

116
Q

what are some things secreted in the primary tubule?

A

anions

urate, penicillin, salicylate, phenobarbital, probenecid

cations

creatinine (felines), cimetidine, morphine

117
Q

Veterinary importance of proximal tubular secretion:

A
  • 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.
118
Q

the distal tubule are important for re-absorption of ___

A

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

119
Q

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

A

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

120
Q

___ are able to reabsorb solutes against a high gradient

A

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

121
Q

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

A

thick ascending loop of henle

salt is reabsorbed but water is not, creates hypertonic (watery) solution

122
Q

explain re-absorption in the thick ascending loop of henle

A

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

123
Q

where does this happen

A

thick ascending loop of henle

(no brush border, basolateral border wavy)

124
Q

how does furosemid work

A

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

125
Q

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

A

principal

intercalated cells

126
Q

what is the main function of the collecting duct

A

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<u>+</u> and its concentration in the urine is determined by efficiency of these two mechanisms.

127
Q

Intercalated cells are involved in___re-absorption. Principal cells are involved in ___ secretion.

where are these cells found?

A

K+ and Na+

K+

collecting duct

128
Q

intercalated cells

A

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.
129
Q

principle cells

A

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
130
Q
A

principle cells in the collecting duct that secrete K

131
Q

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

A

Na+/H+

Na

132
Q

how does ANP effect collecting ducts?

A

atrial natriuretic peptide

increase blood volume= stretch in atria= releases ANP

stimulates the release of Na with urine by inhibiting Na channels

133
Q

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

A

aquaporin

134
Q

___ 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.

A

ANP (atrial natriuetic peptide)

135
Q

third factors increase the excretion of ___

A

sodium (similar to ANP atrial natriuretic peptide)

136
Q

___ 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+.

A

aldosterone

137
Q

how does aldosterone work?

A

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).

138
Q

how is aldosterone triggered

A

low blood pressure (hypotension by angiotensin II)

or

by increased K in plasma (hyperkaliemia)

139
Q

what does aldosterone do to principle cells

A
  • 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
140
Q

what is the net results of aldosterone

A
  • 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
141
Q

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?

A

aldosterone not working

therefore there is high K, low Na and Cl and low blood volume

142
Q

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

A

swell

shrink

143
Q

hyponatremia

A

too low Na+

cerebral edema

144
Q

what controls Na re-absorption in the proximal tubule

A
145
Q

how is Na reabsorbed in the loop of henle

A
146
Q

how is Na reabsorbed in the distal tubule

A
147
Q

how is sodium reabsorbed in the collecting tubules

A
148
Q

3 way to reabsorb Na

A
149
Q

Angiotensin II-aldosterone system – stimulate Na+ ___

A

re-absorption

150
Q

ANP and Third Factor(s) – inhibit Na+ ___

A

re-absorption

151
Q

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.

A

ECF

152
Q

Acidemia (pH<7.4) release of___ by cells into ECF

A

K+

153
Q

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

A

K+

154
Q

K in nephrons

A

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.

155
Q

how is K reabsorbed ?

A

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

156
Q

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

A

thin segment of the loop of henle

157
Q
A

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.

158
Q

in the late distal tubule and collecting duct what controls K

A

K+ secretion by principal cells

K+ reabsorption by intercalated cells

159
Q

principle cells and K+ transport

A

K+ secretion by principal cells-

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+ out of the cell into the tubular lumen

160
Q

intercalated cell and K

A

K reabsorption

•Intercalated cells in outer part of the medullary collecting duct 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.

161
Q

hypokalemic polymyopathy in cats

A

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
162
Q

increased K intake will cause ___

A

increased quantity and activity of Na+,K+-ATPase pumps and amplification of principal cell basolateral membrane.

principal cells are in charge of K secretion

163
Q

how does aldosterone effect K

A

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).

164
Q

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+ ___

A

out of the cell into the tubular lumen

165
Q

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

A

secretion

166
Q

how does H+ balance affect K

A

•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.

167
Q

how does urine flow rate effect K

A

•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+.

168
Q

how do drugs and toxins effect K?

A

•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.

169
Q

•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.

A

ionized

170
Q

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

A

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.

171
Q

what type of calcium can undergo filtration by the kidney?

A

free solutes

protein bound calcium can not fit through the filter

172
Q

how does Calcium, Mg and PO4 get reabsorbed?

A
  • 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
173
Q

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

A
  • 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.
174
Q

most of Mg is reabsorbed where?

A

ascending limb of the loop of henle (60%)

175
Q

•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.

A

thick ascending limb

176
Q

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

A
  • 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 increase Ca2+ excretion makes loop diuretics a key component of therapy for hypercalcemia.
177
Q

how to treat hypercalcemia

A

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

178
Q

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

A

•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.

179
Q

•Approximately __of filtered PO4 is excreted in the final urine

A

20%

180
Q

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

A

10%

181
Q

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

A

•Parathyroid hormone (PTH)

182
Q

PTH is released when

A
  • decreased plasma concentrations of Ca2+
  • decreased plasma concentrations of Mg2+ (up to ~0.8 mg/100 ml)
183
Q

what does PTH inhibits what and stimulates what?

A

Inhibition of PO4 reabsorption in the proximal tubule

  1. 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+

184
Q

the net effect of PTH is the __

A

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

185
Q

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

A

PTH

186
Q

•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.

A

calcitriol

187
Q

Calcitriol does what?

A

• 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.

188
Q

calcium reabsorption in the distal tubule

A

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

189
Q

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

A

~285

190
Q

•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).

A

dilute

concentrated

191
Q

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

A

cardiac

192
Q

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

A

diuresis

193
Q

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

A

osmotic diuresis

194
Q

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

A

water diuresis

195
Q

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

A

Antidiuresis

196
Q

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

A

hypoosmotic

197
Q

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

A

hyperosmotic

198
Q

•___ is responsible for the reabsorption of the bulk of filtered solutes.

A

The proximal tubule

199
Q

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

A

isotonically.

200
Q

•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

A

Na+

201
Q

two ways water is reabsorbed in the proximal tubule

A
  1. through the cells forming the proximal tubule (transcellular pathway)
  2. via solvent drag through the zonae occludae - contacts between these cells (paracellular pathway).
202
Q

•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.

A

oncotic

Starling’s

203
Q

two types of nephrons

A
    1. cortical (with short loop of Henly) - B
    1. medullar (with long loop of Henle) - A
204
Q

would camels have short or long loops of henle

A

long

to get as much water back as possible

205
Q

•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.

A

passive

206
Q

The three components of the urinary concentrating system are:

    1. Countercurrent multiplier system of the ___.
    1. Countercurrent exchange system of the ____.
    1. ____ and its effects on the permeability of the distal tubule and the collecting duct.
A

loop of Henle

vasa recta

Antidiuretic hormone (ADH)

207
Q

what part of the loop of henle is permeable to water

A

descending loop

208
Q

what part of the loop of henle is permeable to Na

A

ascending thin and thick and distal

water can not leave these sections unless aquaporin is added

209
Q

explain countercurrent multiplier

A

•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.

210
Q

•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.

A

osmotic

211
Q

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

A

thin descending limb (TDL)

thin ascending

thick ascending (TAL - impermeable to water)

212
Q

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

A

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

213
Q

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

A

urea

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

214
Q

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

A

hypertonic

215
Q

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

A

vasa recta

216
Q

The vasa recta are specialized peritubular capillaries, which function in ___exchange

A

countercurrent

217
Q

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

A

vasa recta

218
Q

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

A

cortex

219
Q
A

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

220
Q

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

A

vasopressin

221
Q

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

A

peptide

222
Q

ADH is stored and released from neurons in the___pituitary gland.

A

posterior

223
Q

___regulates permeability of collecting ducts to water

A

ADH

224
Q

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

A

impermeable

225
Q

what happens in ADH present in collecting duct

A

ADH allows water to diffuse out into the interstitium

will concentrate urine

226
Q

how does ADH let water out

A

inserts aquaporines into the membrane of the collecting duct

227
Q

ADH and urea

A

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%).

228
Q

proper water balance is based on what two elements?

A
  1. water output (regulated in part by ADH)
  2. water input (regulated through the sensation of thirst and the behavioral response to this sensation)
229
Q

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

A

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

230
Q

Changes in plasma osmolality are monitored by ___ near the hypothalamus

A

osmoreceptors

231
Q

When plasma volume ___and/or plasma osmolality ___, inhibition is relieved and ADH is released into the blood.

A

decreases

increases,

232
Q

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

A

1%

233
Q

how far does plasma volume drop to stimulate ADH release

A

10%

234
Q

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

A

thirst

235
Q

why do horses not drink after exercise

A

lose hypertonic sweat

lose more Na then water

need electrolyte supplement

236
Q

urine more concentrated than glomerular filtrate

A

Hypersthenuria

237
Q

•urine more dilute than glomerular filtrate

A

Hyposthenuria

238
Q

water deprivation test

A

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

239
Q

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.

A

diabetes insipidis (does not produce ADH)

can’t concentrate urine

240
Q

pu/pd

increased glucose

decrease pH, increase CO2, low bicarbonate

A

diabetes

acidosis

241
Q

exercise intolerance, crackles

ph 7.37

PO2 low

PCO2 high

A

pneumonia

respiratory acidosis

242
Q

two ways to get rid of acid

A

H converted to CO2 and H20 and exhales

kidney removes H and HCO in urine

243
Q

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).
A

ECF

ICF and bone

histidine

phosphates

244
Q

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

A

isohydric

pH = pK1 + log ([HCO3-]/[H2CO3]). base/acid

pH = pK2 + log ([protein-]/[Hprotein])

pH = pK3 + log ([HPO42-]/[H2PO4-])

245
Q

bicarb/CO2

A

CO2 + H2O <=> H2CO3 <=> H+ + HCO3-

volatile acid

246
Q

the carbonic H2CO3-HCO3- system is in equilibrium with a gas (CO2), CO2 is called a ___acid

A

volatile

247
Q

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
A

ultrafiltrate

net acid

248
Q

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

A

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

249
Q

The kidneys can generate (produce) new HCO3- through:

  • urinary excretion of ____ salts
  • urinary excretion of ___
A

ammonium (NH4+)

titratable acids.

250
Q

normal HCO3 in the blood

A

24mM

251
Q

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

A

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

252
Q

how is bicarb preserved in the kidney

A

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.

253
Q

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

A

NaHCO3

254
Q

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

A

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

255
Q

high levels of ___stimulate Na+-H+ exchange to promote reabsorption of bicarb in the proximal tubule

A

angiotensin II

256
Q

urinary excretion of ammonium

A
257
Q

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.

A

acute acidosis

258
Q

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.

A

chronic metabolic acidosis

259
Q

excretion of titratable acid

A
260
Q

•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 (HPO42-).

A

phosphate

di-acid

monoacid

261
Q

•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

A

bicarbonate

262
Q

__protonated phosphates are excreted.

A

•Di

(H2PO4-)

263
Q

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).
A

Na+/H+

phosphate

264
Q

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 ____).

A

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.

265
Q

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.

A

NET ACID EXCRETION

266
Q

H secretion in the proximal tubule

A
  • 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 HPO42- to form H2PO4-
267
Q

•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)

A

H+ out pump

and

K in H out pump

268
Q

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

A
  • acidemia*
  • alkalemia*
269
Q

When the pHa 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).

A
  • metabolic acidosis*
  • metabolic alkalosis*
270
Q

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

A

physiologic processes

271
Q

normal amount of PaCO2

normal amount of HCO3

normal blood pH

A

PaCO2=40

HCO3= 24 mM

pH= 7.4

272
Q

will K increase or decrease will acidosis?

A

increase (hyperkalemia)

H will be pulled into cells and K and Na will be pushed out

273
Q

will k increase or decrease with alkalosis?

A

decrease

cell will kick out H and pull in K and Na

leading to hypokalemia

274
Q

what is the pH and HCO3 during acidosis

A

pH, 7.38

bicarb < 22

275
Q

what causes metabolic acidosis

A
  • 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.
276
Q

how to compensate for metabolic acidiosis

A

•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 pHa stimulates lung ventilation (VA), so PaCO2 decreases minimizing the decrease in pHa. For each 1 mM decrease in [HCO3-] a 1 mm Hg drop in PaCO2 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.

277
Q

pH and bicarb for alkalosis?

A

pH >7.42

bicarb >26

278
Q

causes of metabolic alkalosis

A
  • 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.

279
Q

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.

A

Angiotensin II

280
Q

how to compensate for metabolic alkalosis

A

Compensations

•Respiratory. As pHa increases, VA is depressed and PaCO2 increases (PaCO2 > 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 PaCO2.

•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 pHa 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 PaCO2, by ECF volume contraction, by hyperaldosteronism, by K+ depletion, and by hypochloremia. b-intercalated cells in collecting ducts secrete bicarbonate, increasing its urinary excretion.

281
Q

causes of respiratory acidosis

A

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

282
Q

compensation for respiratory acidosis

A

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 PaCO2 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 PaCO2 is high.

283
Q

causes of respiratory alkalosis

A

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

284
Q

compensation for respiratory alkalosis

A

Compensations

•Cell buffers (acute). A decrease in [HCO3-] for decrease in PaCO2 - 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 PaCO2, 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.

22 spring: Physiology (34 decks)

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