Renal System

A&P Exam 4

Direct functions of the kidneys

Regulation of water, inorganic ion balance, acid-base balance

Removal of metabolic waste and foreign chemicals from blood and excreting it in urine

Gluconeogenesis

Hormone production

Define gluconeogenesis

The creation of new glucose from non-glucose substrates

Where does urea and uric acid come from

Byproducts of protein breakdown

Where does bilirubin come from

Hemoglobin, a byproduct of breakdown of heme pigment and produces color derivatives

What hormones/enzymes do the kidneys produce? Explain

Erythropoietin - controls erythrocyte production

Renin - controls formation of angiotensin, which influences blood pressure and sodium balance

Vitamin D - activates it to influence calcium balance

Functional unit of kidney

Nephron

Name these structures

1. Renal artery

2. Renal vein

3. Renal pelvis

4. Ureter

5. Cortex

6. Medulla

7. Papilla

8. Capsule

9. Calyx

Describe the path of blood as it enters and leaves the kidney

Blood comes in from renal artery → dumped off in cortex (filtered) → filtrate moves through medulla in renal pyramids (modified) → dumped into calyx (drainage) → merges at renal pelvis (urine is removed) → clean blood is returned to systemic circulation via renal vein, urine sent to urinary bladder

Name the tubular components of nephron

A. Bowman’s capsule

B. Proximal convoluted tubule

C. Loop of Henle

D. Distal convoluted tubule

E. Collecting duct

Name the vascular components of nephron

A. Renal artery

B. Afferent arteriole

C. Glomerular capillaries

D. Efferent arteriole

E. Peritubular capillaries

F. Renal vein

Name and describe the two types of nephrons

Juxtamedullary (15%) - has long loops of Henle that dip in the medulla, closest to medulla, generates gradient in medulla for H2O reabsorption, peritubular capillaries are called vasa recta

Cortical (85%) - short loops of Henle, don’t contribute to gradient in medulla

What does the renal cortex contain

Outer layer that contains…

• Renal corpuscles of nephrons

• Proximal and distal tubules of all nephrons

• Cortical nephrons

Describe the renal medulla

Inner layer (renal pyramids) that contains…

• Long loops of henle from juxtamedullary nephrons

  • Medullary portion of collecting ducts

Define the juxtaglomerular apparaturs

Specialized region that regulates glomerular filtration rate (GFR) and systemic blood pressure by sensing the amount of NaCl in filtrate

Controls release of renin

List parts of the juxtoglomerular apparatus

Juxtaglomerular cells, macula densa, sympathetic nerve fiber

Explain juxtaglomerular cells

AKA granular cells

Surrounds afferent arterioles

Synthesizes, stores, and secretes renin in response to BP, norepeinephrine, and macula densea

Explain the macula densa

Part of the wall of distal tubule

Senses filtrate flow and sends paracrine signals to afferent arteriole to regulate BP and amount of filtrate produced

Explain the sympathetic nerve fiber

Comes from the VM center, constricts afferent arteriole

Causes renin secretion from JG cells

___% of plasma is filtered; ___% continues into efferent arteriole

20; 80

Excretion formula

= filtered + secreted - reabsorbed

Examples of substances that are all freely filtered but 100% secreted, partially reabsorbed, and 100% reabsorbed

100% secreted - drugs, toxins

Partially reabsorbed - Na+, Cl-, water

100% reabsorbed - glucose, amino acids

Name the three basic renal processes

Glomerular filtration, tubular reabsorption, tubular secretion

Define glomerular filtration

The first step in urine formation where water and small dissolved substances are filtered out of the blood and into Bowman’s capsule, occuring in the glomerulus

What occurs in glomerular filtration

Blood enters glomerulus where afferent arteriole has high pressure → pushes fluid out of blood through a filtration membrane → filtrate enters Bowman’s capsule → leaves to enter proximal tubule

Describe the three layers composing the filtration barrier

Capillary endothelium (fenestrated for more exchange)

Basement membrane (negatively charged matrix)

Bowman’s epithelium (podocytes and filtration slits)

What substances cannot pass the filtration barrier and why

RBCs and plasma proteins because they’re too big to pass through the capillary fenestrations

Small proteins because they are negatively charged and will be repelled by the basement membrane

Explain starling forces involved in glomerular filtration

PGC (usually 60mmHg) - filtrates from glomerular capillary to Bowman’s space

PBS - opposes filtration

πGC - opposes filtration, determined by plasma proteins but usually deosn’t exist

How do renal arterioles regulate PGC

Decreased GFR

• Constricting afferent arteriole

• Dilating efferent arteriole

Increased GFR

• Constricting efferent arteriole

• Dilated afferent arteriole

Net glomerular filtration pressure equation

= PGC - PBS - πGC

Filtered load equation

= GFR x [Ps] (plasma solute)

Excreted load equation

= V (urine flow rate) x [Us] (urine solute)

If filtered load > excreted load, there’s net ____. If filtered load < excreted load, there’s net ____

Reabsorption, secretion

What % of filtered volume is reabsorbed in tubular reabsorption

99

What are the modes of tubular reabsorption

Diffusion and mediated transport

What are the two routes of tubular reabsorption

Transcellular transport - through cell membranes to ISF

Paracellular transport - through tight junctions to ISF

Explain the glucose concentration vs filtered load, reabsorption, excretion graph

Filtered load is normal, reabsorption keeps up with filtration at low plasma solute concentrations

Solute in urine with high plasma concentration will reabsorb but reach a transport maximum

Explain tubular secretion

Usually involves active transport but diffusion can occur

Occurs in proximal tubules

Also reaches a transport maximum

Define renal plasma clearance

The volume of plasma cleared of a specific substance per unit time. Higher RPC means the kidneys are removing more of that substance from the plasma

What does RPC tell us in relation to GRF

= GFR - everything filtered is secreted (ex. inulin)

< GFR - clearance is close to 0 mL, partially reabsorbed substances are filtered

> GFR - active secreted into tubule, almost everything is filtered

What muscles are involved in micturition. What’s their type and activity during filling and micturition

Detrusor - parasympathetic - inhibited - stimulated

Internal urethral sphincter - sympathetic - stimulated - inhibited

External urethral sphincter - somatic motor - stimulated inhibited

What are two main points about total-body balance of water

For homeostasis to be maintained, intake must equal output

Urine is the main regulator for intake to match output

What are the proportions of total-body fluid

NaCl prop ECF volume prop MAP

What are the typical values of volumes in the body

Plasma - 3L, ISF - 11L, ICF - 28L

What do osmoreceptors detect

ECF osmolarity and its changes due to pure gains in water

Water distributes itself equally across all membranes so most goes into cells

What do baroreceptors detect

Pressure changes in the ECF due to pure gains in NaCl

NaCl stays in ECF and needs pumps

How does water move across the three fluid compartments

After drinking water, there’s more H2O in the plasma → bulk flow to ISF → lower tonicity so water goes to ICF

How does NaCl move across the three fluid compartments

Add excess NaCl, greater osmolarity → net diffusion to ISF → NaCl stays in ISF, making it hypertonic → water moves from ICF to ISF → water leaving makes ECF greater in volume → more plasma volume and higher MAP

____ moves with sodium

Chloride ; to help maintain electroneutrality

Na+ and H2O are ____ filtered at the glomerulus and _____ reabsorbed with ____ secretion

Freely; mostly; no

What percentage of water and sodium is reabsorbed

99% each

Describe the mechanism of Na+ reabsorption in the proximal tube

Na+ enters capillary via Na+/K+ ATPase, creates gradient

Na+ enters cell via cotransport with X or countertransport with H+

• Basolateral needs X and K+ channels

Describe the mechanism of Na+ reabsorption in the ascending limb of the loop of henle

Na+/K+ ATPase takes Na+ out to capillary, creates gradient

Na+ comes in through NKCC channel

• Basolateral needs K+ and Cl- channels

• Apical needs K+ channel

Describe the mechanism of Na+ reabsorption in the cortical collecting duct

Na+/K+ ATPase creates gradient

Na+ and K+ channels in the apical membrane

How much Na+ reabsorption occurs in each location and is it regulated

Proximal tubule - 65%, non regulated

Ascending limb - 25%, non regulated

Cortical collecting duct - 10%, regulated by aldosterone

Define aldosterone

A steroid hormone that builds more Na+ and K+ channels and Na+/K+ ATPases

What are the water route types and where do they occur

Paracellular - main water route in proximal tubule (65%)

Transcellular - main water route in collecting ducts where it requires aquaporins

Define ADH

Vasopressin

Induces aquaporin insertion into apical membranes of collecting duct, increasing water reabsorption

Increases permeability of urea by activating urea transporters, regulates osmolarity

Explain ADH mechanism

ADH is secreted from plasma → binds to receptor on basolateral → signal cascade → AQP2 vesicle with aquaporins fuses to apical membrane → more water transport → higher water reabsoprtion

Define and explain the renal medullary gradient

A gradual increase in osmolarity of kidney tissue from cortex to inner medulla

• Only juxtamedullary nephrons with long loops of Henle create the gradient

• Created by countercurrent multiplier system and urea recycling

• Vasa recta circulation maintains the gradient

Explain the concurrent multiplier system of juxtamedullary nephrons

Filtrate enters loop from proximal tubule →

Descending limb, permeable to water but not NaCl →

Bottom of loop equilibrates (is most osmotic) →

Ascending limb, impermeable to water and pumps NaCl via NKCC → flows out

Multiplier due to the increasing osmolarity as fluid goes down and then decreasing osmolarity as it goes up

Explain urea recycling

Urea is filtered at glomerulus → water leaves in proximal tubule and descending limb, making urea more concentrated → filtrate reaches medullary collecting duct → ADH increases permeability of urea → accumulates in medulla → some diffuses into loop of henle → flows to duct again and recycles

How does the vasa recta maintain the renal medullary gradient

Reabsorbs water and solutes to circulation without washing out gradient, exchanges between ascending and descending

Has extremely small blood flow

Describe the two ways of regulating renal sodium

Regulating the filtered load by changing GFR (less common, occurs with large MAP change)

Regulating the rate of reabsorption (more common, for both large MAP change and differences in ingestion)

Explain control of GFR to regulate renal sodium

A decrease in plasma volume lowers GFR, reducing H2O and Na+ excretion, kidneys want to retain it

Explain the RAAS control of renal sodium

When JG cells sense ↓ BP, ↓ fluid volume, ↑ B1 sympathetic → kidneys secrete renin, activating angiotensinogen into angiotensin I

ACE converted angiotensin I into angiotensin II which increases vasoconstriction and aldosterone release (more Na+ and H2O retention) → both increases blood pressure

Explain common hypertension medications

ACE inhibitors - block conversion of angiotensin I → angiotensin II

Ang II blockers - blocks angiotensin II from binding to receptors, stops vasoconstriction

Aldosterone receptor blockers

Define atrial natriuretic peptide (ANP)

Secreted when increases plasma volume and MAP causes distension of atria

The anti-aldosterone, alters arterioles to increase GFR and increase Na+ excretion

Explain osmoreceptor control of ADH when extra-hydrated vs dehydrated

Extra-hydrated - lower osmolarity → lower firing of osmoreceptors → less ADH → less permeability and H2O reabsorption → more H2O excretion

Dehydrated - higher osmolarity → higher firing of osmoreceptors → more ADH → more permeability and H2O reabsorption → less H2O excretion

Explain baroreceptor control of ADH (low plasma vol)

Low plasma volume → low blood vessel pressures → baroreceptors stretch and fire less → posterior pituitary releases ADH → increases H2O permeability and reabsorption → less H2O excretion

Define diabetes mellitus

Osmotic diuresis

Failure to reabsorb glucose → huge amount of glucose in urine causes H2O to be retained in urine due to osmotic following of glucose

Define diabetes insipidus

Water diuresis

Failure of posterior pituitary to release ADH or failure of kidney to respond to ADH → H2O permeability is low, increased water loss

How does sweating affect excretion

Sweat contains H2O and NaCl and loses hypoosmotic salt solution

• Lowers plasma volume → lowers Na+ excretion

• Increases plasma osmolarity → increases ADH → less H2O excretion

What are some things that lead to thirst

• Dry mouth/throat

• Metering of water intake by GI tract

• Increased plasma osmolarity

• Decreased blood volume

How does caffeine and alcohol affect the renal system

Caffeine dilates afferent arterioles

Alcohol inhibits ADH secretion

Both cause the loss of more water

What are the intracellular and extracellular fluid [K+] controlled by + values

Intracellular - Na+/K+ ATPase (150 mM)

Extracellular - kidneys (5mM)

What are the ions that experience filtration, reabsorption, and secretion

K+ and Cl-

Describe reabsorption of K+ in the proximal tube

It is reabsorbed paracellarly by following H2O into the ISF and into the capillary

65% of K+ reabsorption occurs here

Describe reabsorption of K+ in the ascending loop of Henle

K+ is reabsorbed with the NKCC transporter. Cotransports in with the Cl- and goes through a leak channel into the capillary

Describe regulation of K+ in the coritcal collecting duct

There is K+ secretion as Na+/K+ ATPase is in the basolateral and apical membranes.

K+ follows a gradient from ISF → duct cells → tubular lumen

Regulated by aldosterone

Summarize aldosterone control of Na+ and K+

Aldosterone increases due to…

• ↓ Plasma volume → ↑ angiotensin II

• ↑ Plasma K+

Then inserts more K+ and Na+ channels, allowing for Na+ reabsorption and K+ excretion

Summarize the functions of each part of the renal tubules

Glomerulus/Bowman’s capsule - filtration of plasma

Proximal tubule - bulk reabsorption, secretion of solutes

Loop of Henle - establishes medullary osmotic gradient

• Descending - bulk reabsorption of water

• Ascending - reabsorption of Na+ and Cl-

Cortical collecting duct - fine tuning of reabsorption/secretion

What is the normal pH in the body

7.4

How does respiration and the kidneys adjust pH

Respiration - rapidly adjusts pH by changing CO2 levels

Kidneys - slowly adjusts pH by changing bicarb levels

What are sources of hydrogen ion gain?

• From CO2

• Catabolism of organic molecules

• Loss of bicarb in diarrhea or urine

What are sources of hydrogen ion loss?

• Anabolism of organic anions

• Loss of H+ in vomit (stomach acid = HCl)

• Loss in urine

• Hyperventilation

How much bicarbonate is reabsorbed at rest

100%

Explain how bicarb is reabsorbed in the proximal convoluted tubule

H2O + CO2 makes bicarb + H+

Bicarb → capillary

H+ → lumen → combines with a filtered bicarb in lumen to make H2O and CO2 → that CO2 can go back into the cell to start over process

How do you make more bicarb using HPO42-

H2O + CO2 makes bicarb + H+

Bicarb → capillary

H+ → lumen → combines with filtered HPO42- → H2PO4- → excreted

Simultaneously removes acidity and creates more buffer in capillary

How do you make new bicarb with glutamine and ammonium

Glutamine enters cell either from

• Capillary

• Filtered in through lumen, cotransports with Na

→ breaks down into NH4+ and bicarb → bicarb goes to capillary → NH4- goes out, Na+ goes in via countertransporter → NH4+ is excreted

Removes acid (NH4+)

Describe cause, result, and compensation of respiratory acidosis

Cause: ↑ CO2 (hypoventilation)

Result: ↑ H+

Compensation: renal makes ↑ bicarb

Describe cause, result, and compensation of respiratory alkalosis

Cause: ↓ CO2 (hyperventilation)

Result: ↓ H+

Compensation: renal makes ↓ bicarb (excretes)

Describe cause, result, and compensation of metabolic acidosis

Cause: ↑ H+ (from more lactic acid or loss of bicarb in diarrhea)

Result: ↓ bicarb

Compensation: more ventilation to ↓ CO2

Describe cause, result, and compensation of metabolic alkalosis

Cause: ↓ H+ (vomiting)

Result: ↑ bicarb

Compensation: less ventilation to ↑ CO2