Ch 17

Physiology of

the Kidneys

Review Anatomy on your own

SLOs • List and describe the 4 major functions of the kidneys.

• List and explain the 4 processes of the urinary system.

• Diagram the filtration barriers a H2O molecule will pass as it travels from the blood into the nephron and illustrate the anatomical structures and mechanisms by which filtration can be controlled.

• Define GFR and give the average value for GFR.

• Describe the hydrostatic and osmotic pressures that contribute to glomerular filtration and indicate the direction of fluid movement favored by the net pressure.

• Diagram how GFR can be influenced by: – variable resistance in afferent and efferent renal arterioles. – myogenic and tubuloglomerular autoregulatory mechanisms. – hormonal control and neural control.

• Describe active and secondary active transport and passive reabsorption mechanisms used by the kidney to accomplish reabsorption of Na+ and glucose.

• Create a generalized graph of the reabsorption of glucose in order to demonstrate how protein-mediated renal transport can reach saturation. Mark on the graph where transport maximum and renal threshold occur.

• Explain the connection between GFR and Clearance rate and explain clinical significance of the clearance

• Apply the equation E = F – R + S to analyze renal handling of a substance.

• Diagram the involuntary micturition reflex and incorporate the voluntary control influence exerted by higher brain centers.

17.1 FUNCTION OF THE KIDNEYS

Kidneys function in …

H2O & solute concentration homeostasis

ECF volume ( BP)

osmolarity, electrolyte concentration

pH homeostasis (acid-base balance)

Excretion of wastes & foreign

substances

Hormone and enzyme production

Functional unit?

Four Processes of Urinary System

1. Filtration

2. Reabsorption

3. Secretion

4. Excretion

Related by equation:

E = F - R + S

180 L / day filtered, >99% reabsorbed,

1.5 L / day excreted

Fig 19-4

17.2 GLOMERULAR FILTRATION = Movement of fluid from blood to lumen of

nephron (rel. nonspecific process)

Capillaries are ____________

Once in lumen: Considered outside body

Composition of filtrate?

Glomerular Ultrafiltrate: Passage Across 3 Barriers

1. ____________________

2. ____________________

3. ____________________

Some small molecules (Ca2+, low m.w. fatty acids)

bind to plasma proteins ?

Compare to Fig 17-9

3 Types of Pressures Influence Filtration

1. Hydrostatic pressure in capillaries

2. Colloid osmotic pressure

3. Hydrostatic pressure in Bowman’s capsule

Net driving

pressure ?

Glomerular Filtration Rate = GFR

Describes filtration efficiency: Amount of fluid filtered per unit of time

Average GFR ?

Total blood volume is filtered every 40 minutes

Most must be reabsorbed immediately

Fig 17-10

GFR Closely Regulated … to remain constant over wide range of MAPs (70 - 180 mm Hg)

Goal is to control blood flow through afferent and efferent arterioles

RBF ?

PH ?

GFR ?

vasodilation

GFR Regulation either via

1. Renal Autoregulation

– myogenic

– tubuloglomerular feedback

2.Reflex regulation

– NS

– Hormones (e.g.: angiotensin II and prostaglandins)

17.3 TUBULAR REABSORPTION H2O reabsorption via osmosis (PCT and CD

Electrolyte reabsorption highly selective and variable

Mostly transepithelial transport (examples: Na+ and glucose)

Reabsorption may be active (Na+, glucose) or passive (urea)

Na+

Reabsorption in Proximal Tubule

PCT and LOH Reabsorption

• 65% of salt and water reabsorbed in PCT

• An additional 20% reabsorbed in LOH

• Happens continuously and is unregulated

• Final 15% of water ( 27 L) ab- sorbed in CD under hormonal control

• Fluid entering loop of Henle is isotonic to extracellular fluids

Countercurrent Multiplier not covered!

Reabsorption in LOH

Fig 17-14

Renal Medulla Creates Concentrated Urine

Reabsorption of varying amounts of H2O and Na+ established by LOH and CD

How is H2O absorbed? Only by _______________ due to the high medullary interstitial osmolarity

Key player: ADH = ____________, or________

• Body fluid osmolarity : ________? • Urine osmolarity can vary from 50 to 1200 mOsm.

Released from? when?

Controls water permeability of last section of DCT and all of CD

Regulates aquaporin channels

How?

ADH regulated via 1. ECF osmolarity 2. BP and BV

Collecting Duct: Effect of ADH

ADH Stimulation of Aquaporin Channels

Fig 17-19

Diabetes insipidus

Nocturnal enuresis

Clinical Application

A. Neurogenic / Central:

B. Nephrogenic:

C. Also: Dipsogenic and gestational

Desmopressin for A and C

Concentrated vs. Dilute Urine In presence of ADH:

Insertion of H2O pores

At maximal H2O permeability: Net H2O movement stops at equilibrium

Maximum osmolarity of urine?

No ADH:

DCT & CD impermeable to H2O

Osmolarity can plunge to ~ 50 mOsm

Review:

ADH No ADH

17.4 RENAL PLASMA CLEARANCE Kidneys must also remove excess ions and wastes from the blood Renal Clearance

• GFR begins this process

• Reabsorption returns some substances to blood (decreases renal clearance)

• Secretion moves substances from peritubular capillaries into tubules (increases renal clearance)

Fig 17.21

Clinical Importance of GFR and Clearance

GFR is indicator for overall kidney function

Clearance → non-invasive way to measure/estimate GFR (creatinine and inulin)

If substance is filtered and reabsorbed but not secreted clearance rate > or ?< GFR

If substance is filtered and secreted but not reabsorbed clearance rate > or ?< GFR

Inulin used as markers of glomerular filtration rate because it is filtered but not reabsorbed or secreted

Easier to use Creatinine

Mechanism of Reabsorption

in the PCT

Complete reabsorption in PCT via

1. 2 active transport with sodium = ______

2. facilitated diffusion =_____

3. simple diffusion

Fig 17.24

Reabsorption of Glucose

Na+

linked Glucose Reabsorption in Proximal Tubule

Characteristics of Renal Transport

As in all mediated transport

Transport maximum determined by

1. Specificity

2. Competition

3. Saturation Renal threshold, determines transport maximum.

Copyright © 2010 Pearson Education, Inc.

Saturation of Mediated Transport

Fig 19-9

Copyright © 2010 Pearson Education, Inc.

Glucose Handling by the Nephron

Fig 19-10

Glycosuria

Diabetes mellitus Untreated DM → high blood glucose levels → …

→ Osmotic Diuresis

→ Polyuria and polydipsia

Similarities and

differences to

diabetes insipidus ?

Secretion

2nd route of entry into tubules for selected molecules

Mostly transepithelial transport (analogous to reabsorption). Depends mostly on membrane transport systems (usually 2o active transport)

Provides mechanism for rapid removal of substances . Most important for H+, K+, foreign organic ions and drugs such as penicillin etc.)

Excretion = Urine Output Excretion of H2O, excess ions, nitrogenous waste,

toxins, and other foreign molecules

Depends on F, R, S (formula ?)

Direct measurement of F, R, S impossible infer from blood & urine analysis

Kidneys clean or “clear” plasma of certain substances

For any substance: Clearance = plasma volume completely cleared of that substance per minute

Micturition Reflex

Spinal cord integration: 2 simultaneous efferent signals

Infant: Simple spinal reflex

Later: Learned reflex under conscious control from higher brain centers

Various subconscious factors affect reflex

Fig 19-14

17.5 RENAL CONTROL OF ACID-BASE BALANCE

• Kidneys maintain blood pH by reabsorbing bicarbonate and secreting H+.

• Normal urine pH?

Fig 17.29

Acid–Base Balance • Normal blood pH ?

• Enzymes & NS very sensitive to pH changes

• Kidneys have K+/H+ antiporter

• Importance of hyperkalemia and hypokalemia

• Acidosis vs. alkalosis

Fig 20-14

Acidosis Respiratory acidosis due to alveolar hypoventilation

→ accumulation of ______

Possible causes: Respiratory depression, increased airway resistance (___________), impaired gas exchange (___________, ______________, _____________ ____________, _______________________________)

Metabolic acidosis due to gain of fixed acid or loss of bicarbonate

Possible causes: lactic acidosis, ketoacidosis, diarrhea

Buffer capabilities exceeded once pH change appears in plasma. Options for compensation?

3 Mechanisms to Deal with pH Changes

Buffers 1st defense, immediate response

Ventilation 2nd line of defense, can handle ~ 75% of most pH disturbances

Renal regulation of H+ & HCO3-

final defense, slow but very effective

Renal Compensation for Acidosis Reabsorption of HCO3

- and Secretion of H+

Compare to Fig 17.29

Alkalosis much rarer

Respiratory alkalosis due to alveolar hyperventilation in the absence of increased metabolic CO2 production

Possible causes: Anxiety with hysterical hyperventilation, excessive artificial ventilation, aspirin toxicity, fever, high altitude

Compensation?

Metabolic alkalosis due to loss of H+ ions or shift of H+ into the intracellular space.

Possible causes: Vomiting or nasogastric (NG) suction; antacid overdose

Compensation?

Renal Failure & Artificial Kidney

Symptoms when < 25% functional nephrons

Causes

1. Chronic: Diabetes, HBP

2. Acute:

1. Kidney infections

2. Chemical poisoning (lead, paint-thinner) etc.

Hemodialysis:

3/week 4-8h/session

CAPD Alternative:

Continuous Ambulatory Peritoneal Dialysis