Pathophysiology II Exam 4: Renal System

ways in which the renal system regulates homeostasis

• removes waste and toxins (medications)

• regulates body’s fluid, electrolyte, acid-base balance

• releases hormones that regulate BP and Ca2+

• produce active forms of Vitamin D

• controls production of RBCs

location of glomerulus of nephrons

renal cortex

how much blood flows through kidneys each minute

1200 mL

blood flow through kidney in order

• renal artery

• afferent arteriole

• glomerulus

• efferent arteriole

• peritubular capillary

• renal vein

arteriole entering glomerulus

afferent arteriole

arteriole leaving glomerulus

efferent arteriole

if a patient has less than ___ nephrons, dialysis is required

360,000

urinary excretion rate

glomerular filtration + tubular secretion - tubular reabsorption

in nephrons, filtration occurs in the

glomerulus

what kind of capillary is the glomerulus

fenestrated

in order for a substance to enter renal tubules, it must pass through in order

• fenestrated epithelium of glomerular capillary

• basement membrane

• podocytes (foot processes)

function of nephrin

transmembrane protein that supports structure of podocytes

main determinant of what gets filtered through the glomerulus

podocytes (foot processes)

size of pores in the fenestrated epithelium of the glomerulus capillary

large, 70-100 nm in diameter

function of heparin sulfate in the basement membrane of glomerulus

protein filtration via charge: blocks negatively charged proteins like albumin

function of type IV collagen and laminin in the basement membrane of glomerulus

protein filtration by size: blocks large proteins like albumin

area between epithelial podocytes is called

slit diaphragm/filtration slits

what does not get filtered through glomerulus

RBCs and proteins

ions, drugs, toxins are actively pumped into

distal tubule

increased renal perfusion pressure (BP) causes

increased sodium and water excretion, reduced extracellular fluid returns blood pressure back to normal

renin-angiotensin-aldosterone system (RAAS) in controlling blood pressure

increased BP inhibits RAAS axis, reducing the vasoconstrictor effects of angiotensin II, decreases solute resorption in proximal and distal tubules

Natriuresis

Na+ excretion from the kidneys

what promotes natriuresis

ventricular and atrial natriuretic peptides, calcitonin

what inhibits natriuresis

aldosterone

where is angiotensinogen secreted

the liver

what converts angiotensinogen to angiotensin I

renin from the kidney, released by a decrease in renal perfusion

what converts angiotensin I to angiotensin II

ACE from lungs and kidney

effect of angiotensin II on nervous system

increases sympathetic activity

effect of angiotensin II on kidney

increased tubular Na+ and Cl- resorption, K+ secretion, water retention

effect of angiotensin II on adrenal gland

increased aldosterone secretion

effect of angiotensin II on BP

arteriolar vasoconstriction, increased BP

effect of angiotensin II on pituitary gland

increased ADH secretion

what inhibits renin secretion form the kidney

water and salt retention, effects of angiotensin II (negative feedback)

ADH effect on distal tubule and collecting duct

increases permeability by inserting more aquaporins, more water reabsorbed

alcohol effects on ADH

inhibits ADH release from pituitary

caffeine effects on ADH

interferes with ADH activity

hydrostatic pressure in glomerulus

higher than other capillary beds, 50 mmHg

nutrients (salts, amino acids, vitamins, etc.) are moved out of nephron tubules via

active transport

water is moved out of nephron tubules via

osmosis

some ions, drugs (antibiotics, beta blockers, digoxin), and toxins are secreted into distal tubule via

active transport

what is secreted out of the collecting duct

water and urea

why is a high sodium, low potassium diet problematic

Na+ is actively recovered in the renal system, K+ is pumped out. high sodium diet disrupts this equilibrium, causes HTN

how does the kidney regulate blood pressure

increased renal perfusion BP leads to a rise in sodium and water excretion, decreasing blood volume and BP (pressure natriuresis)

relationship between RAAS and pressure natriuresis

increased BP inhibits the RAAS axis, reducing the vasoconstrictor effects of angiotensin II on afferent arterioles, decreasing solute reabsorption in nephron

effects of ADH (vasopressin)

more water retained in the kidneys, increases permeability of the distal tubule and collecting duct by inserting more aquaporins into the membrane

alcohol and caffeine are classified as

diuretics

extrinsic control of arterial diameter

sympathetic nervous system

continuous capillary

• most common, least permeable

• intercellular clefts and transcellular cytosis allows for exchange of molecules

• abundant in skin and muscle

fenestrated capillary

• pores in the endothelial membrane

• found in the kidney

sinusoidal/discontinuous capillary

• most permeable and least common

• big holes in the endothelial membrane, big clefts between cells

• seen in liver, spleen, bone marrow

pathways of movement of water and solutes across capillaries

• paracellular via endothelial pores

• transcellular directly through the cell membrane via vesicles

exchange of small macromolecules through capillary

• smaller molecules can diffuse through interendothelial clefts through fenestrae <1 nm in diameter

• positively charged molecules are more permeable than negative

• most plasma proteins have a negative charge

exchange of large macromolecules through capillary

• macromolecules with diameter > 1 nm can cross at a very slow rate through intercellular clefts, fenestrations, paracellular gaps

• transcellular transcytosis via vesicles is predominant pathway

diffusion of water and solutes through capillary: via endothelial pores (paracellular pathway)

• the determinant of permeability (more junction proteins means decreased pores/pore size and decreased diffusion/permeability)

• mostly water and ions

diffusion of water and solutes through capillary: via vesicular transport (transcellular pathway)

• plasmalemmal vesicles transport large polar molecules

• transport of larger polar molecules

diffusion of water and solutes through capillary: through the cell membrane (transcellular pathway)

• water moves through aquaporin 1 (AQP1) channels

• ions move through specific channels down their concentration gradients or via carriers like Na+/K+ATPase

• any nonpolar substance can move directly through cell membrane

Js in Fick’s law of diffusion

net flux of a solute through the capillary membrane (moles/cm²/s)

Px in Fick’s law of diffusion

the ease with which a solute passes the endothelium (cm/sec)

Cp in Fick’s law of diffusion

concentration of solute in capillary

Ci in Fick’s law of diffusion

concentration of solute in interstitial space

how to calculate Px

product of diffusion coefficient and surface area divided by distance

net hydrostatic pressure

Pc - Pi

Capillary hydrostatic pressure: Pc

force pushing fluid out of capillaries, avg 35 mmHg at arteriole end and 15 mmHg venous end

Interstitial hydrostatic pressure: Pi

opposes fluid movement out of capillary, ranges from 0 to -7 mmHg

hydrostatic pressure (P)

pressure exerted by blood against the wall of capillary, force that drives fluid out of capillaries and into interstitial tissues, aka capillary blood pressure

oncotic pressure (π)

osmotic pressure generated by large molecules (especially proteins like albumin) in the blood plasma or interstitial fluid, aka colloid osmotic pressure

capillary plasma oncotic pressure: πc

pulling force plasma protein to keep fluid in vessel, 25 mmHg throughout the capillary

interstitial oncotic pressure: πi

pulls water out of capillary and into interstitium, avg 0 mmHg at arteriole end and 4 mmHg at venous end

Jv in Starling’s equation

trans endothelial solvent filtration volume per second

when Jv > 0

net movement of fluid out of vessel into interstitial fluid

when Jv < 0

net movement of fluid into vessel form interstitium

σ in Starling’s equation

reflection coefficient, the fraction of plasma and interstitial proteins which can pass across the endothelium

when σ = 0

vessel completely permeable to protein, freely filtrable

when σ = 1

proteins can’t cross the endothelium, completely reflected (i.e. BBB)

Kf in Starling’s equation

filtration coefficient, the relative permeability of the membrane overall (normal renal Kf = 12.5 mL/min/mmHg)

what structural component is most important to Kf (filtration coefficient)

number of junctional adhesion complexes

where is Pc higher than πc

at the arteriolar end

where is πc higher than Pc

at the venular end

hallmarks of intestinal mucosa capillary

absorption the entire length, Pc < < < πc

hallmarks of glomerular capillary

filtration the entire length, Pc > > > πc

effects of histamine on vasculature

• increased Pc and Kf causes increased Jv

• arteriole dilation and venous constriction, more blood in capillaries

• decreased arteriole resistance, increased venous resistance

total lymph flow

2-3 L/day, about 2 L/min

functions of the lymphatic system

• removing large particulate matter from interstitial space

• regulates interstitial fluid volume and pressure

expansion phase in lymph valve

interstitial pressure exceeds that in the collecting lymphatic, lymph moves in

compression phase in lymph valve

hydrostatic pressure inside initial lymphatic rises, closing the microvalves and moving lymph further downstream the collecting lymphatic, via skeletal muscle contraction and intestinal peristalsis

where does lymph empty into venous circulation

subclavian veins

What is Acute Kidney Injury (AKI)?

Abrupt loss of kidney function within a few days.

What percentage of adults in the United States are estimated to have chronic kidney disease?

More than 15% of adults, or more than 37 million people.

What is the characteristic of acute renal pathophysiology?

Reversible nephron damage; kidney function can return to normal.

What are the three types of acute renal pathophysiology?

Pre-renal, Intra-renal (Intrinsic), Post-renal.

What is the characteristic of chronic renal pathophysiology?

Permanent damage to nephrons.

What is a common cause of chronic renal pathophysiology?

Diabetic kidney disease.

What is the final stage of chronic renal disease?

End-stage renal disease.

What treatment is commonly used for end-stage renal disease?

Dialysis.

What is a marker of renal disease related to urine output?

Low urine output (oliguria)

What is a marker of renal disease related to kidney function?

Low GFR

What is a marker of renal disease indicated by blood tests?

High serum creatinine

What electrolyte imbalance is a marker of renal disease?

Hypocalcemia

What electrolyte imbalance is associated with renal disease?

Hypokalemia

What is a marker of renal disease that involves cystatin?

Elevated cystatin C