Physiology Of The Kidney

Front 1

What is the function of the kidney?

Back 1

1.To regulate plasma and interstitual fluid by formation of urine
2. Also regulates
- volume of blood plasma (contribute to BP),
- waste products in blood
- concentration of electrolytes (Na,K,HCO3)
- and plasma pH

Front 2

Describe the structure of the urinary system?

Back 2

1.paired kidneys are on either side of vertebral column below diaphragm
2. Urine flows from kidneys into ureters which empty into bladder

Front 3

Name and describe some of the major structures in the kidney?

Back 3

1. Cortex - contains many capillaries and outer parts of nephrons
2. Medulla-consists of renal pyramids separated by renal columns
3. Renal Pyramid contains minor calyces which unite to form a major calyx
4. Major calyces join to form renal pelvis which collects urine
5. Conducts urine to ureters which empty into bladder

Front 4

What is the detrusor muscle?

Back 4

smooth muscle wall in the bladder

Front 5

What causes Micturition Reflex (Urination)?

Back 5

1. Filling of bladder activates stretch receptors that send impulses to micturition reflex center
2. This activates Parasymp neurons causing contraction of detrusor muscle that relaxes internal urethral sphincter creating sense of urgency
There is voluntary control over external urethral sphincter
3. When urination is consciously initiated, descending motor tracts to micturition center inhibit somatic motor fibers of external urethral sphincter and urine is expelled

Front 6

What regulates the action of internal and external urethral sphincters?

Back 6

1. reflex center located in sacral part of cord

Front 7

What do drugs for overactive bladders target?

Back 7

muscarinic receptors

Front 8

What is a nephron?

Back 8

1. Is functional unit of kidney; responsible for forming urine
>1 million nephrons/kidney
2. Is a long tube and has associated blood vessels

Front 9

Describe the path through the Renal blood vessels.

Back 9

1. Blood enters kidney through renal artery- interlobar arteries- arcuate arteries - interlobular arteries- afferent arterioles which supply glomeruli
2. Efferent arteriole drains glomerulus and delivers that blood to peritubular capillaries (vasa recta)
Blood from peritubular capillaries enters veins

Front 10

What are Glomeruli?

Back 10

A mass of capillaries inside glomerular capsule that gives rise to filtrate that enters nephron tubule

Front 11

What are Nephron tubules and where do they end?

Back 11

1. Tubule begins with glomerular capsule which transitions into proximal convoluted tubule (PCT), then to descending and ascending limbs of Loop of Henle (LH), and distal convoluted tubule (DCT)
2. Tubule ends where it empties into collecting duct (CD)

Front 12

What is the function of the Glomerular (Bowman's) Capsule.

Back 12

1.Surrounds glomerulus
2. Together they form renal corpuscle
Is where glomerular filtration occurs
3. Filtrate passes into PCT

Front 13

What is the Proximal Convoluted Tubule(PCT)

Back 13

Walls consist of single layer of cuboidal cells with millions of microvilli
Which increase surface area for reabsorption

Front 14

What are the two types of nephrons and describe them.

Back 14

1. Cortical nephrons originate in outer 2/3 of cortex
2. Juxtamedullary nephrons originate in inner 1/3 cortex
Have long LHs
Important in producing concentrated urine

Front 15

What does fenestrated mean?

Back 15

have large pores between its endothelial cells

Front 16

What are some of the main components of Glomerular Filtration?

Back 16

1. Glomerular capillaries and Bowman's capsule form a filter for blood
2. Glomerular Caps are fenestrated--have large pores between its endothelial cells
Big enough to allow any plasma molecule to pass
100-400 times more permeable than other Caps
3,To enter tubule filtrate must pass through narrow slit diaphragms formed between pedicels (foot processes) of podocytes of glomerular capsule

Front 17

What is proteinuria?

Back 17

In some diseases, a lot of protein appears in the urine

Front 18

What is the effect of glomerular filtration on proteins?

Back 18

1. Plasma proteins are mostly excluded from the filtrate because of large size and negative charge
2. The slit diaphragms are lined with negative charges which repel negatively-charged proteins
3. Some protein (especially albumin) normally enters the filtrate but most is reabsorbed by receptor-mediated endocytosis

Front 19

What is Glomerular Ultrafiltrate?

Back 19

Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure

Front 20

What is the Glomerular Filtration Rate (GFR)?

Back 20

1. Is volume of filtrate produced by both kidneys/min
2. Averages 115 ml/min in women; 125 ml/min in men
3. Totals about 180L/day (45 gallons)
4. So most filtered water must be reabsorbed or death would ensue from water lost through urination

Front 21

What regulates the Glomerular filtration rate?

Back 21

1. Is controlled by extrinsic and intrinsic (autoregulation) mechanisms
2. Vasoconstriction or dilation of afferent arterioles affects rate of blood flow to glomeruli and thus GFR

Front 22

What are the sympathetic effects on glomerular filtration rate?

Back 22

1. Sympathetic activity constricts afferent arteriole
2. Helps maintain BP and shunts blood to heart and muscles
3. Decreases GFR

Front 23

Describe Renal Autoregulation?

Back 23

1. Allows kidney to maintain a constant GFR over wide range of BPs
2. Achieved via effects of locally produced chemicals on afferent arterioles
3. When average BP drops to 70 mm Hg afferent arteriole dilates
4. When average BP increases, afferent arterioles constrict
5. Increased flow of filtrate sensed by macula densa (part of juxtaglomerular apparatus) in thick ascending LH
Signals afferent arterioles to constrict

Front 24

What is tubuloglomerular feedback.

Back 24

negative feedback between afferent arteriole and volume of filtrate maintains autoregulation

Front 25

What is the function of PCT?

Back 25

1. returns most molecules and H2O from filtrate back to peritubular capillaries
2, About 180 L/day of ultrafiltrate produced; only 1–2 L of urine excreted/24 hours
3. Urine volume varies according to needs of body

Front 26

What is reabsorbtion?

Back 26

Return of filtered molecules

Front 27

How is water reabsorbed?

Back 27

1. Water is never transported
Other molecules are transported and water follows by osmosis
2. Filtrate in PCT is isosmotic to blood (300 mOsm/L)
3. Thus reabsorption of H2O by osmosis cannot occur without active transport (AT)
4. Is achieved by AT of Na+ out of filtrate Loss of + charges causes Cl- to passively follow Na+
Water follows salt by osmosis

Front 28

What is obligatory water loss?

Back 28

Minimum of 400 ml/day urine necessary to excrete metabolic wastes

Front 29

What is the significance of PCT reabsorbtion?

Back 29

~65% Na+, Cl-, and H2O is reabsorbed in PCT and returned to bloodstream
An additional 20% is reabsorbed in descending loop of Henle
Thus 85% of filtered H2O and salt are reabsorbed early in tubule
This is constant and independent of hydration levels
Energy cost is 6% of calories consumed at rest
The remaining 15% is reabsorbed variably, depending on level of hydration

Front 30

Describe the concentration gradient of the kidney?

Back 30

1. In order for H2O to be reabsorbed, interstitial fluid must be hypertonic
2. Osmolality of medulla interstitial fluid (1200-1400 mOsm) is 4X that of cortex and plasma (300 mOsm)
3. This concentration gradient results largely from loop of Henle which allows interaction between descending and ascending limbs

Front 31

Describe the Descending Limb of the Loop Henle(LH).

Back 31

1. Is permeable to H2O
2. Is impermeable to, and does not AT, salt
3. Because deep regions of medulla are 1400 m Osm,
4. H2O diffuses out of filtrate until it equilibrates with interstitial fluid
5. This H2O is reabsorbed by capillaries

Front 32

Describe the Ascending Limb of the Loop Henle(LH).

Back 32

1. Has a thin segment in depths of medulla and thick part toward cortex
2. Impermeable to H2O; permeable to salt; thick part ATs salt out of filtrate
3. AT of salt causes filtrate to become dilute (100 mOsm) by end of LH

Front 33

How does active transport play a role in the ascending limb?

Back 33

1. NaCl is actively extruded from thick ascending limb into interstitial fluid
2. Na+ diffuses into tubular cell with secondary active transport of K+ and Cl-
3. Occurs at a ratio of 1 Na+ and 1 K+ to 2 Cl-
4. Na+ is AT across basolateral membrane by Na+/ K+ pump
5. Cl- passively follows Na+ down electrical gradient
6. K+ passively diffuses back into filtrate

Front 34

Describe the Countercurrent Multiplier System.

Back 34

1. Countercurrent flow and proximity allow descending and ascending limbs of LH to interact in way that causes osmolality to build in medulla
2. Salt pumped out of thick ascending part raises osmolality around descending limb, causing more H2O to diffuse out of filtrate
3. This raises osmolality of filtrate in descending limb which causes more concentrated filtrate to be delivered to ascending limb
4. As this concentrated filtrate is subjected to AT of salts, it causes even higher osmolality around descending limb (positive feedback)
5. Process repeats until equilibrium is reached when osmolality of medulla is 1400

Front 35

What is the vasa recta?

Back 35

1. Is important component of countercurrent multiplier
Permeable to salt, H2O (via aquaporins), and urea
2. Recirculates salt, trapping some in medulla interstitial fluid
3. Reabsorbs H2O coming out of descending limb
4. Descending section has urea transporters
5. Ascending section has fenestrated capillaries

Front 36

What are the effects of Urea on the Kidney?

Back 36

1. Urea contributes to high osmolality in medulla
2. Deep region of collecting duct is permeable to urea and transports it

Front 37

What is the role of the collecting duct?

Back 37

1. Plays important role in water conservation
2. Is impermeable to salt in medulla
3. Permeability to H2O depends on levels of ADH

Front 38

What is the role of ADH?

Back 38

1. Is secreted by post pituitary in response to dehydration
2. Stimulates insertion of aquaporins (water channels) into plasma membrane of CD
3. When ADH is high, H2O is drawn out of CD by high osmolality of interstitial fluid
4. And reabsorbed by vasa recta

Front 39

What is renal clearance?

Back 39

1. Refers to ability of kidney to remove substances from blood and excrete them in urine
2. Occurs by filtration and by secretion
3. Secretion is opposite of reabsorption--substances from vasa recta are transported into tubule and excreted
4. Reabsorption decreases renal clearance; secretion increases clearance

Front 40

What is the excretion rate=?

Back 40

(filtration rate + secretion rate) - reabsorption rate

Front 41

Describe the secretion of drugs in the kidney?

Back 41

1. Many drugs, toxins, and metabolites are secreted by membrane transporters in the PCT
2. These transport organic anion and cation molecules
3. And determine the half-life of many therapeutic drugs
4. Many foreign molecules (xenobiotics) are eliminated by this system at a more rapid rate than by glomerular filtration

Front 42

What is Inulin?

Back 42

a fructose polymer, is useful for measuring GFR because is neither reabsorbed or secreted

Front 43

How do they calculate Rate at which a substance is filtered by the glomeruli?

Back 43

Quantity filtered (mg/min) = GFR (ml/min) x P (mg/ml)
P = inulin concentration in plasma (mg/ml)
Quantity excreted = V x U
V = rate of urine formation (ml/min); U = inulin concentration in urine (mg/ml)
Amount filtered = amount excreted
GFR = (V x U)/P

Front 44

What is renal plasma clearance?

Back 44

1. Is volume of plasma from which a substance is completely removed/min by excretion in urine
2. If substance is filtered but not reabsorbed then all filtered will be excreted RPC = GFR
3. If substance is filtered and reabsorbed then RPC < GFR
If substance is filtered but also secreted and excreted then RPC will be > GFR (=120 ml/ min)
RPC = (V*U)/P

Front 45

Describe the clearance of urea?

Back 45

1. Urea is freely filtered into glomerular capsule
2. Urea clearance calculations demonstrate how kidney handles a substance: RPC = V X U/P
V = 2ml/min; U = 7.5 mg/ml of urea; P = 0.2 mg/ml of urea
RPC = (2ml/min)(7.5mg/ml)/(0.2mg/ml) = 75ml/min
3. Urea clearance is 75 ml/min, compared to clearance of inulin (120 ml/min)
4. Thus 40-60% of filtered urea is always reabsorbed
5. Is passive process because of presence of carriers for facilitative diffusion of urea

Front 46

What is done with blood not filtered by the glomerular capsule?

Back 46

1.Not all blood delivered to glomerulus is filtered into glomerular capsule
2. 20% is filtered; rest passes into efferent arteriole and back into circulation
3. Substances that aren't filtered can still be cleared by active transport (secretion) into tubules

Front 47

How is total renal blood flow measured?

Back 47

PAH clearance is used to measure total renal blood flow
Normally averages 625 ml/min
It is totally cleared by a single pass through a nephron
So it must be both filtered and secreted
Filtration and secretion clear only molecules dissolved in plasma
To get total renal blood flow, amount of blood occupied by erythrocytes must be taken into account
45% blood is RBCs; 55% is plasma
 total renal blood flow = PAH clearance
= 625/0.55 = 1.1L/min 0.55

Front 48

Describe the Glucose and Amino Acid Reabsorption in the kidney?

Back 48

1. Filtered glucose and amino acids are normally 100% reabsorbed from filtrate
2. Occurs in PCT by carrier-mediated cotransport with Na+
3. Transporter displays saturation if ligand concentration in filtrate is too high
4. Level needed to saturate carriers and achieve maximum transport rate is transport maximum (Tm)
5. Glucose and amino acid transporters don't saturate under normal conditions

Front 49

What is Glycosuria and what are its effects on the body?

Back 49

1. Is presence of glucose in urine
Occurs when glucose > 180-200mg/100ml plasma (= renal plasma threshold)
2. Glucose is normally absent because plasma levels stay below this value
3. Hyperglycemia has to exceed renal plasma threshold
4. Diabetes mellitus occurs when hyperglycemia results in glycosuria

Front 50

How does the kidney manage electrolyte balance?

Back 50

1. Kidneys regulate levels of Na+, K+, H+, HCO3-, Cl-, and PO4-3 by matching excretion to ingestion
2. Control of plasma Na+ is important in regulation of blood volume and pressure
3. Control of plasma of K+ is important in proper function of cardiac and skeletal muscles

Front 51

What is the Role of Aldosterone in Na+/K+ Balance?

Back 51

1. 90% filtered Na+ and K+ reabsorbed before DCT
2. Remaining is variably reabsorbed in DCT and cortical CD according to bodily needs
3. Regulated by aldosterone (controls K+ secretion and Na+ reabsorption)
4. In the absence of aldosterone, 80% of remaining Na+ is reabsorbed in DCT and cortical CD
5. When aldosterone is high all remaining Na+ is reabsorbed

Front 52

Describe K+ Secretion in the kidney?

Back 52

1. Is only way K+ ends up in urine
2. Is directed by aldosterone and occurs in DCT and cortical CD
3. High K+ or low Na+ will increase aldosterone and K+ secretion

Front 53

What is the Juxtaglomerular Apparatus (JGA)?

Back 53

Is specialized region in each nephron where afferent arteriole comes in contact with thick ascending limb LH

Front 54

Describe the Renin-Angiotensin-Aldosterone System?

Back 54

1. Is activated by release of renin from granular cells within afferent arteriole
2. Renin converts angiotensinogen to angiotensin I
3. Which is converted to Angio II by angiotensin-converting enzyme (ACE) in lungs
4. Angio II stimulates release of aldosterone

Front 55

Describe the Regulation of Renin Secretion?

Back 55

1. Inadequate intake of NaCl always causes decreased blood volume
2. Because lower osmolality inhibits ADH, causing less H2O reabsorption
3. Low blood volume and renal blood flow stimulate renin release
4. Via direct effects of BP on granular cells and by Symp activity initiated by arterial baroreceptor reflex (see Fig 14.26)

Front 56

What is the Macula Densa?

Back 56

1. Is region of ascending limb in contact with afferent arteriole
2. Cells respond to levels of Na+ in filtrate
3. Inhibit renin secretion when Na+ levels are high
4. Causing less aldosterone secretion, more Na+ excretion

Front 57

What is Atrial Natriuretic Peptide (ANP)?

Back 57

1. Is produced by atria due to stretching of walls
2. Acts opposite to aldosterone
3. Stimulates salt and H2O excretion
4. Acts as an endogenous diuretic

Front 58

What is the Na+, K+, and H+ Relationship?

Back 58

1.Na+ reabsorption in DCT and CD creates electrical gradient for H+ and K+ secretion
2. When extracellular H+ increases, H+ moves into cells causing K+ to diffuse out and vice versa
3. Hyperkalemia can cause acidosis
4. In severe acidosis, H+ is secreted at expense of K+

Front 59

Describe Renal Acid-Base Regulation?

Back 59

1. Kidneys help regulate blood pH by excreting H+ and/or reabsorbing HCO3-
2. Most H+ secretion occurs across walls of PCT in exchange for Na+ (Na+/H+ antiporter)
3. Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HCO3- and excrete H+

Front 60

Is Reabsorption of HCO3- in PCT indirect or direct and why?

Back 60

1. Is indirect because apical membranes of PCT cells are impermeable to HCO3-
2. When urine is acidic, HCO3- combines with H+ to form H2CO3 (catalyzed by CA on apical membrane of PCT cells)
2. H2CO3 dissociates into CO2 + H2O
3. CO2 diffuses into PCT cell and forms H2CO3 (catalyzed by CA)
4. H2CO3 splits into HCO3- and H+ ; HCO3- diffuses into blood

Front 61

What are the effects of Urinary Buffers?

Back 61

1. Nephron cannot produce urine with pH < 4.5
2. Excretes more H+ by buffering H+s with HPO4-2 or NH3 before excretion
3. Phosphate enters tubule during filtration
4. Ammonia produced in tubule by deaminating amino acids
Buffering reactions
HPO4-2 + H+  H2PO4-
NH3 + H+  NH4+ (ammonium ion)