EXAM 4 - Renal Phys Part 1

Major Components of the renal system

◻ Kidneys (2) ◻ Ureters (2) ◻ Bladder ◻ Urethra

Functions of the renal system:

In the process of making & excreting urine....

In the process of making & excreting urine....

⬜ 1. remove metabolic waste

⬜ 2. maintain homeostasis - ion and electrolyte balance

⬜ 3. Regulate total body water

⬜ 4. Control pH of body fluids

⬜ 5. Gluconeogenesis

⬜ 6. Control of arterial pressure

⬜ 7. Excretion of foreign chemicals

⬜ 8. Secretion, metabolism, and excretion of

hormones - EPO, vitD, renin

Excretion of Metabolic Waste Products

urea

uric acid

creatinine

bilirubin

urea

byproduct of protein metabolism

uric acid

byproduct of nucleic acid metabolism

creatinine

byproduct of muscle metabolism

bilirubin

byproduct of RBC metabolism

Excretion of Foreign Chemicals

drugs (prescription and drugs from abuse), toxins (spider bite), pesticides, food additives

Hormones produced by the kidney

erythropoietin (EPO) and 1,25 dihydroxycholecalciferol (vitamin D)

Hormones metabolized & excreted by kidney

most peptide hormones (insulin, angiotensin II, prolactin, GH)

Regulation of Erythrocyte Production

-Kidneys filter the blood and indirectly measuring the oxygen level in the blood being delivered to kidneys

-WHEN O2 delivery to kidneys are low: Secrete the hormone erythropoietin which acts on the bone marrow to make more RBC (erythrocyte production)

Gluconeogenesis

kidneys synthesize glucose from amino acids during times of stress

during prolonged fasting leads to this

this is very minor

Regulation of Water and Electrolyte Balances

• Sodium and Water

• Potassium- important to maintain heart rhythms

• Hydrogen Ions

• Calcium, Phosphate, Magnesium

Regulation of Arterial Pressure

Endocrine Organs

1. RAA system

2. Kalikrein - enzyme that converts prorenin into renin...facilitates RAA

3. prostaglandins

Control of Extracellular Fluid Volume (ADH)

Volume of Filtrate Produced is based on

1. volume of fluid ingested

2. water of metabolism (water made during metabolism)

MINUS:

3. evaporation loss at the lungs

4. sweating (skin)

5. fecal loss

filtrate

fluid that passes from the blood through the capillary walls of the glomeruli of the kidney = urine

main function of the kidney

removal of wast from the blood

nephron

functional unit of the kidney (portion that does physiology)

each kidney contains 1 million

types of nephrons

cortical nephrons and juxtamedullary nephrons

cortical nephrons

located in cortex

function in waste removal

juxtamedullary nephrons

-located in cortex and dig deep into medulla (long nephron loop digging deep)

Function: waste removal, control of volume and concentration of urine

Nephron composed of 5 parts

renal corpuscle

proximal convoluted tubule

loop of henle

distal convoluted tubule

collecting duct

Renal corpuscle

glomerulus and bowman's capsule

glomerulus

A ball of capillaries surrounded by Bowman's capsule in the nephron

Function: filtration - "sieve"

-collect RBC, WBC, etc and save it while the fluid goes through

Bowmans capsule

encases the glomerulus and collects the filtrate

proximal convoluted tubule (PCT)

segment of the nephron between the glomerular capsule and the nephron loop

reabsorbs (save) majority (99.999%) of substances

SAVE:

protein, glucose, etc

in a diseased state this can be impaired and will not save the good stuff

Loop of Henle (LOH)

the nephron loop

Function: works to concentrate the filtrate- using countercurrent multiplier

distal convoluted tubule (DCT)

functions to adjust the final concentration of Na+ by Aldosterone

collecting duct (CD)

functions to adjust the final H2O volume via ADH

Renal Blood Flow

renal artery

--> interlobar artery

--> arcuate artery

--> interlobular artery

--> afferent arteriole*

--> glomerulus*

--> efferent arteriole*

--> peritubular capillaries*

--> interlobular vein

--> arcuate vein

--> interlobar vein

renal vein

urine formation is based on 3 nephron processes

filtration, reabsorption and secretion

where does the majority of the filtration occur

renal corpuscle (glomerulus)

where does the majority of the reabsorption occur

reabsorption= save back into the body

majority at PCT

where does the majority of the secretion occur

secretion= get rid of from body

majority occurs at DCT

Basic Mechanisms of Urine Formation

1= filtration

2= reabsorption

3= secrete

4= excrete

excretion = what

filtration - reabsorption + secretion

Renal Handling of Different Substances

1. filtration only

2. filtration and partial reabsorption

3. filtration, and complete reabsorption

4. filtration and secretion

Renal Handling of Water

save almost all water

EX: filter 180L, reabsorption of 179L - so 1L excreted

Renal Handling of sodium

save almost all Na+ (important to regulate osmolarity)

EX: filter 25,560 mmol/day, reabsorption of 25410 mmol/day - so 150 excreted (mmol/day)

Renal Handling of glucose

reabsorb al of it- shouldnt have glucose in urine

EX: filter 180, reabsorption of 180 - so 0 excreted (gm/day)

Renal Handling of creatinine

excrete all- creatine is a byproduct of muscle metabolism that is constantly made as well as being a waste product...want to get rid of it

EX: filter 1.8, reabsorption of 0 - so 1.8 excreted (gm/day)

Filtration facts about filtration of the blood volume

1. 20% of blood flows through the kidneys each minute

- about 1200 ml/min

100% of blood volume goes through kidneys in 5 min

Volume of filtrate formed each minute

glomerular filtration rate (GFR)

- 125ml/min

Anatomical features for filtration of glomerulus

glomerular capillaries fenestrated

special basement membrane

specialized cells

Glomerular capillaries

Fenestrated (holes) vessels that allow passage of all plasma elements but not blood cells.

Special basement membrane of glomerulus

allows glomerulus to filter out (save) large proteins - antibodies as an example are proteins and are important to save

Specialized cells of the glomerulus

podocytes - save smaller proteins

GFR

125 ml/min = 180 liters/day

Plasma volume is filtered ___ times per day

60

Glomerular filtrate composition is about the same as _____, except for _____

plasma, large proteins

filtrate doesn't contain large proteins- podocytes and the basement membrane prevent proteins

Filtration fraction

(GFR/Renal Plasma Flow)= 0.2 (i.e., 20% of plasma is filtered each minute)

about 120/600

Filtration Dynamics

◻ Based on 3 Pressures:

1. Glomerular Hydrostatic Pressure

2. capsular Hydrostatic Pressure

3. Glomerular Plasma Colloid Osmotic Pressure

Glomerular Hydrostatic Pressure

P in the glomerulus

Favors filration

equals = 60 mmHg

capsular Hydrostatic Pressure

P in Bowmans capsule

opposes filtration

equals 18mmHg

cannot be more than 60 mmHg if you want any filtration

Glomerular Plasma Colloid Osmotic Pressure

opposes filtration

equals 32 mmHg

net filtration pressure

1. Glomerular Hydrostatic Pressure (60) - capsular Hydrostatic Pressure (18) - Glomerular Plasma Colloid Osmotic Pressure (32)

equals 10 mmHg

Calculation of Net Filtration Pressure (NFP)

NFP= P(favor)-P(oppose)

- differences between the favoring and opposing pressures

forces that favor = 60 mmHg

forces that oppose filtration = 18 + 32 mmHg = 50

60-50 = 10 mmHg

***it is a low pressure, but it is positive therefore will be favoring filtration!!

Control of Glomerular Filtration

driving pressure is glomerular hydrostatic pressure

GFR is autoregulated

what does it mean for the GFR to be autoregulated

it means we will maintain a normal GFR (125ml/min) despite changes in BP - autoregulation isnt instant (beat to beat) but it will within 2-3 minutes

what does it mean if we do not autoregulate? (high and low BP example)

if we do not do this:

1. high BP - increase Net filtration pressure, increase GFR, increase in urine volume - DEHYDRATES

2. low BP - low NFP therefore low GFR and low urine output = toxic; not removing metabolic wastes

example: diabetes mellitus

Normal Values:

GFR = ___

Net Filt. Press = ___

Kf = ___

Normal Values:

GFR = 125 ml/min

Net Filt. Press = 10 mmHg

Kf

Glomerular Capillary Filtration Coefficient (Kf)

Kf = hydraulic conductivity x SA

• Normally not highly variable (stable)

Disease that can reduce Kf and GFR

- chronic hypertension

- obesity/diabetes mellitus

- glomerulonephritis

Bowman's Capsule Hydrostatic Pressure (PB)

Normally changes as a function of GFR, not a physiologic regulator of GFR (reacts to changes in GFR but does not causes change to GFR)

changes/reacts to these that change GFR:

• Tubular Obstruction

• Urinary tract obstruction

Tubular Obstruction

kidney stones and tubular necrosis

Urinary tract obstruction

Prostate hypertrophy/cancer

Glomerular Capillary Oncotic Pressure (ΠG)

glomerular colloid osmotic pressure (opposing pressure in glomerulus)

Factors Influencing Glomerular

Capillary Oncotic Pressure (ΠG)

• Arterial Plasma Oncotic Pressure (ΠA)

increase in ΠA will increase ΠG

• Filtration Fraction (FF)

increase in FF will increase ΠG

(Recall: FF = GFR/Renal plasma flow = 125/650 ~ 0.2 (or 20%)

Net Filtration Pressure Decreases Along the Glomerulus Because of

Increasing Glomerular Colloid Osmotic Pressure

net filtration pressure is not equal throughout the glomerulus...it is an average of what is happening in glomerulus

(14+6=20, 20/2= 10mmHg)

Glomerular Hydrostatic Pressure (PG)

**Is the determinant of GFR most subject

to physiologic control*** we can alter/manipulate to change GFR

this is the driving force (the pressure the favors filtration...60mmHg)

Factors that influence PG

- arterial pressure (effect is buffered

by autoregulation...within 2-3 minutes autocorrects)

- afferent arteriolar resistance

- efferent arteriolar resistance

vasoconstriction or dilation to adjust to BP changes

Effect of Afferent and Efferent Arteriolar Constriction on Glomerular Pressure

increasing resistance in the afferent arteriole will decrease blood flow and decrease PG and decrease GFR

increasing resistance in the efferent arteriole (=close off the exit) will increase blood flow and will increase Pg and increase GFR

increase diameter of afferent arteriole

increase GFR

decrease diameter of efferent arteriole

increase GFR

Increase renal a. P

alters overall blood flow (increased)= increase GFR

this subsides in 2-3 minutes

increase PB and ΠG

decrease GFR

increase PG

increase GFR

Determinants of Renal Blood Flow (RBF) equation

RBF = ΔP/R

ΔP = difference between renal artery pressure and renal vein pressure

R = total renal vascular resistance

= Ra + Re + Rv = sum of all resistances in kidney vasculature

Renal Blood Flow - high blood flow

• High blood flow (~22% of cardiac output)

• High blood flow needed for high GFR

Renal Blood Flow - O2 and the nutrients delivered

• Oxygen and nutrients delivered to kidneys normally greatly exceeds the kidneys metabolic needs

• A large fraction of renal oxygen consumption is related to renal tubular sodium reabsorption

Control of GFR & RBF: extrinsic control

Via ANS:

SNS & PSNS

Control of GFR & RBF: intrinsic control

within the kidney

example: increased BP = stretch afferent arteriole leading to vasoconstriction, decreased blood flow, and decreased GFR

vasoconstriction of afferent and efferent arterioles

SNS (Catecholamines) - Control of GFR & Renal Blood Flow

increase the resistance in afferent arteriole which decreases GFR and decreases renal blood flow

-increased vasoconstriction in afferent arteriole

during a severe hemorrhage

AT II on - Control of GFR & Renal Blood Flow

vasoconstrictor

increase resistance of the efferent arteriole

no change in GFR and decrease renal blood flow

**prevents a decrease in GFR - keeping it level (no change)

THERE ARE NO RECEPTORS ON THE AFFERENT ARTERIOLE FOR ATII and afferent arteriole will compensate

examples: low sodium diet and volume depletion

Prostaglandins - Control of GFR & Renal Blood Flow

decrease Resistance on afferent and efferent arteriole

increase GFR and lots of increased renal blood flow

NSAIDS

Heart failure

liver cirrhosis

Summary of Neurohumoral Control of GFR and Renal Blood Flow

Local (Intrinsic) Control of GFR & Renal Blood Flow

◻ "Myogenic" (self regulated) Mechanism

◻ Based on Macula Densa Feedback

◻ ATII-powerful vasoconstrictor

-renal autoregulation for 125ml/min: if BP drops, then GFR falls instantly but over 2-3 minutes, the GFR goes back to 125mlmin (mechanism is not instantaneous)

Macula densa feedback mechanism for regulating GFR

notice that AT II only causes vasoconstriction of efferent arteriole, not afferent arteriole. the afferent arteriole can compensate via other mechanisms so that the decreased arterial pressure doesnt impact on GFR

Other Factors That Influence GFR

• Fever, pyrogens - increase GFR - initially but auto regulate back to normal

• Glucorticoids - increase GFR - initially but auto regulate back to normal

• Aging - decrease GFR (starting at age 40)

• Hyperglycemia - increase GFR

• Dietary protein - high = increase GFR; low = decrease GFR