BIO 116- A&P Exam 4

Urine Formation

180 L fluid processed daily; only 1.5 L → urine

Glomerular filtration

Tubular reabsorption

Tubular secreation

Glomerular filtration

produces cell and protein-free filtrate

Porous membrane filters the blood

Only water and solutes smaller than proteins can pass

Normally NO CELLS should pass

Refers to the filtration of the blood!!

Tubular reabsorption

returns 99% of substances from filtrate to blood in renal tubules and collecting ducts

Tubular secretion

Selectively moves substances from blood to filtrate in renal tubules and collecting ducts

Function 1 of the Nephron

Glomerular Filtration

Layers of the Filtration Membrane

Fenestrated endothelium of glomerular capillaries

Basement membrane (fused basal laminae of two layers)

Foot processes of podocytes with filtration slits; slit diaphragms repel macromolecules

Pressures that Affect FIltration

Hydrostatic pressure in glomerular capillaries

Hydrostatic pressure in capsular space

Colloid osmotic pressure in capillaries

Hydrostatic pressure in glomerular capillaries

= 55mm Hg

Chief force pushing water out, pushes solutes out of blood

Hydrostatic prssure in capsular space

HP_cs Pressure of filtrate in capsule

15 mm Hg

Pushes solutes into the blood

Colloid osmotic pressure in capillaries

OP_gc

The “pulling” by proteins in blood

30 mm Hg

Pushes solutes into the blood

Glomerular Filtration Rate (GFR) and regulation of the Blood Pressure

Volume of filtrate formed per minute by both kidneys ( normal = 120-125 ml/min)

Net filtration pressure (NFP) is a major regularor of GFR

GFR affects systemic blood pressure

Kidneys regulate arterial blood pressure

Norepinephrine and Epinephrine → indue systemic vasoconstriction → increased blood pressure

Constriction of afferent arterioles → down GFR → less urine → increased blood volume and pressure

GFR Affects Systemic Blood Pressure

Up GFR → Up urine output → Down blood pressure

Down GFR → Down urine output → Up Blood pressure

How Kidents regulate arterial blood pressure

1. Direct renal mechanism

2. The renin-angiotensin-aldosterone mechanism

Norepinephrine

Released by sympathetic nervous system

Epinephrine

Released by adrenal medullea

Renin-Anfiotensin-Aldosterone Mechanism

Main mechanism for increasing blood pressure

Three pathways to RENIN release by granular cells

Three pathways to RENIN release by granular cells

Direct stimulation of granular cells by sympathetic nervous system

Stimulation by activated macula densa cells when filreate NaCl is low

Reduced stretch of Granular cells

Function 2 of the Nephron

Reabsorption

Nephron Reabsorption

Major sites are the tubules and collected ducts

All nutrients, e.g., glucose and amino acids, 65% of Na⁺ and water, ion, uric acid; ½ urea (which is later secreted back into filtrate)

They move from the tubule back to the blood (they are reabsorbed).

They come back into the blood!!

Reabsorption of Sodium

Activation of the Na⁺ -K⁺ ATPase pump

Secondary active transport

Facilitated diffusion (apical)

Secondary active transport

a ion couple with another that is transported actively

Apical Facilited diffusion

Happening through proteins binding in the membrane

It doesn’t require energy

Reabsorption of Water

osmosis, aided by water-filled pores calls aquaporins that could open or close

Reabsorption of water in Descending limb

H₂O can leave and solutes cannot

Reabsorption of water in Ascending limb

H₂O cannot leave and solutes can

Reabsorption of organic nutrients

water, glucose, amino acids, some ions, and vitamins

Secondary active transport; cotransport with Na⁺

Water-soluble substances, some ion and urea, follow the water

Lipid-soluble drugs, environmental pollutants are difficult to be reabsorbed because they don’t follow water

Reabsorption is hormonally regulated by:

Antidiuretic hormone (ADH)

Aldosterone

Atrial natriuretic peptide (ANP)

Parathyroid hormone

Antidiuretic hormone (ADH)

increases the reabsorption of water

Aldosterone

Increases the reabsorption of Na⁺ (therefore water)

Atrial natriuretic peptide (ANP)

Decreases reabsorption of Na⁺

Parathyroid hormone

Incresase the absorption of Ca²⁺

Function 3 of the Nephron

Tubular Secretion

Tubular Secretion

K⁺, H₄⁺, HCO₃^- creatinine, organic acids and bases move from peritubular capillaries to the tubule cells into the urinary filtrate:

Solutes move INTO the tubules

They go into the urine. They are secreted.

Functions of Tubular Secretion

Disposes of substances (e.g., drugs) bound to plasma proteins

Eliminates undesirable substances passively reabsorbed (e.g., urea and uric acid)

Rids body of excess K⁺

Controls blood pH by altering amounts of H⁺ or HCO₃^- in urine

Regulation of Urine Concentration and Volume

Kidneys maintain osmolality of plasma at ~300 milliosmoles (mOsm) by regulating urine concentration and volume

How to Kidneys Regulate Urine Concentration and Volume

Use a countercurrent mechanism that maintains two compartments with different osmolarities

A low osmolarity area in the outer medulla

A high osmolarity area located in the inner medulla

How do kidneys maintain two areas with different concentrations of solutes in the medulla area?

The permeability for water and solutes changes at different segments fot he nephron loop

Descending Limb

Freely permeable to H₂O

H₂O leaves attracted by the concentrated medulla → filtrate becomes MORE CONCENTRATED (~1200 mOsm)

Ascending Limb

Impermeable to H₂O

Water stays in the tubule Na⁺ and Cl^- are reabsorbed in thick segment; some passively reabsorbed in thin segment → filtrate becomes LESS CONCENTRATED (100 mOsm)

Vasa Recta

Straight capillaries in the medulla running parallel to the loop

Preserve medullary gradient (different concentrations)

Prevent rapid removal of salt from interstitial space

Remove, reabsorbed water, maintaining the high concentrated medulla

How does the Recycling of Urea helps to maintain the Medullary Osmotic Gradient?

1. Urea is secreted into the ascending limb

2. Urea is reabsorbed in the collecting ducts

3. The urea now is in the medulla maintaining the high concentration gradient

Dilution and Concentration of Urine (Overhydration)

Produces large volume of diluted urine

ADH production decreases → urine ~100 mOsm (less concentrated)

If aldosterone present, additional ions (Na⁺) removed → ~ 50 mOsm (even less concentrated)

Dilution and Concentration of Urine (Dehydration)

Small volume and concentrated urine

When ADH is released (urine ~ 1200 mOsm). The kidney produces less volume and more concentrated urine

In severe dehydration — 99% water is reabsorbed

What is Renal Clearance?

Volume of plasma cleaned by the kidneys of a particular substance in a given time. Ex. Cretinti clearance

Detects glomerular damage and follow up of renal disease

Chronic renal disease

Renal Failure

Chronic renal disease

Defined when GFR < 60 mL/min for 3 months (normal is 120 mL/min)

Renal Failure

GR < 15 mL/min

Causes uremic syndrome

Diuretics

Chemical that enhance urinary output

• ADH inhibitors, alcohol

• Na⁺ reabsorption inhibitors, caffeine, drugs for hypertension or edema

• Loop diuretics they inhibit medullary gradient formation: furosemide (Lasix)

• Osmotic diuretics

Osmotic diuretics

THese substances are not reabsorbed in the tubules and keep and attract water inside tubules (high glucose in diabetic patient, mannitol)

Uremia syndrome

Accumulation of urea and other waste products in the bloodstream, which are normally eliminated by the kidneys

Intracellular fluid (ICF) compartment

Fluid inside cells (2/3 of total body fluid)

Contains more soluble proteins than plasma

• Low Na⁺ and Cl^-

• Major cation: K⁺

• Major anion HPO₄^2-

Extracellular fluid (ECF) compartment

Fluid in two main ECF compartments outside cells

1. Plasma: 3L

2. Interstitial fluid (IF): 12L in spaces between cells

Less proteins than ICF

• Major catio: Na⁺

• Major anion: Cl^-

Fluid Movement among Compartments

Osmotic and hydrostatic pressures regulate change in solute concentration of any compartment

• Increased ECF osmolality → water leaves cell

• Decreased ECF osmolality → water enters cell

• Osmolality is maintained around 280-300 mOsm

Body Water Content

Infants are 73% or more water (low body fat, low bone mass)

Adult males: ~60% water

Adult females: ~50% water (because higher fat content, less skeletal muscle mass)

• adipose tissue is least hydrated of all

• Total body water in adults ~40L

Water content declines to ~45% in old age

Regulation of Water Output

Obligatory water losses → explain why we cannot live without water very long

• Insensible water loss from lungs (respiration) or skin (evaporation)

• Sensible water loss from urine to excrete wastes (60%), obvious sweat (8%), ans feces (4%)

Volume of urine excreted and concentration also depend on fluid intake, diet, and water loss via other avenues

Excessive loss of H₂O from ECF

ECF osmotic pressure rises

Cells lose H₂O to ECF by osmosis → cells shrink

Hypotonic hydration

Cellular overhydration, or water intoxication

Occurs with renal insufficiency or rapid excess water ingestion

ECF osmolality decreases, causing hyponatremia

Treated with hypertonic saline solution

Hyponatremia

Results in net osmosis of water into tissue cells and swelling of cells

Symptoms: severe metabolic disturbances, nausea, vomiting, muscular cramping, cerebral edema, and possible death

Excessive H₂O enters the ECF

ECF osmotic pressure falls

H₂O moves into cells by osmosis → cells swells

Central Role of Sodium in Fluid and Electrolyte Balance

Sodium, is most abundant cation in ECF. It is the only cation exerting significant osmotic pressure

Influence of other hormones

Concentration of Na⁺

Determines osmolality of ECF and excitability of neurons and muscles

Content of Na⁺

Total body content determines ECF volume and therefore blood pressure

Hormones that Regulate Sodium Balance

Estrogens

Progesterone

Glucocorticoids

Estrogens

Increase NaCl reabsorption (like aldosterone)

Leads to H₂O retention during menstrual cycles and pregnancy

Progesterone

Decreases Na⁺ reabsorption (blocks aldosterone)

Promotes Na⁺and H₂O loss

Glucocorticoids

In

Importance of Potassium ans Regulation of Potassium Balance

Affects resting membrane potential (RMP) in neurons and muscle cells (especially cardiac muscles)

Disruption in [K⁺] (hyper-or hypokalemia) in heart can interfere with electrical conduction leading to sudden death

K⁺ is also part of the body’s buffer system

H⁺ shifts in and out of cells in opposite direction of K⁺ to maintain cation balance

Hyperkalemia

Increases in ECF [K⁺]

Cause decreased resting membrane potential, causing depolarization, followed by reduced excitability

Hypokalemia

Decreases in ECF [K⁺]

Cause hyperpolarization and no responsiveness

H⁺ shifts in and out of cells in opposite direction of K⁺ to maintain cation balance, so:

ECF K⁺ levels rise with acidosis

ECF K⁺ levels fall with alkalosis

K⁺ is secreted in the collecting tubes according to the needs of the body

Low K⁺ diet or accelerated K⁺ loss reduces its secretion and promotes its limited reabsorption

Increased K⁺ in adrenal cortex causes release of aldosterone, which increases K⁺ secretion

Regulation of Calcium

99% of body’s calcium is found in bones as calcium phosphate salts

Calcium balance controlled by parathyroid hormone (PTH)

PTH promotes increase in calcium levels by targeting

Bones

Kidneys

Small intestine

Bones and Calcium

Osteoclasts break down matrix, releasing calcium and phosphate to blood

Kidneys and Calcium

Increases calcium reabsorption

Decreases phosphate ion reabsorption

Small Intertine and Calcium

Increases calcium absorption (indirectly by simulation by vitamin D precursor)

Ca²⁺ in ECF is important for:

Blood clotting

Cell membrane permeability

Secretory activities

Neuromuscular excitability: most important

Hypocalcemia

Increases neuromuscular excitability and can lead to muscle tetany

Hypercalcemia

Inhibits neurons and muscle cells and may cause heart arrhythmias

Normal pH of body fluids

Arterial blood: pH 7.4

Venous blood and interstitial fluid: pH 7.35

ICF: pH 7.0

Alkalosis or alkalemia

arterial pH > 7.45

Acidosis or acidemia

arterial pH <7.35

Mechanisms of Concentration of Hydrogen Ions

Chemical buffer systems

Brainstem respiratory centers

Renal mechanisms

Chemical buffer systems

Rapid

First line of defense

Brainstem respiratory centers

Acts within 1-3 minutes

Renal mechanisms

Most potent, but require hours to days to effect pH changes

Chemical Buffer Systmes

A system of one or more compounds that act to resist pH changes when stronf acid or base is added

• Will bine H⁺ if pH drops of release H⁺ if pH rises

There major buffering systems

Bicarbonate buffer system

Phosphate buffer system

Protein buffer system

Respiratory and renal systems

physiological buffering systems

Respiratory system

Eliminates CO₂ (an acid)

During CO₂ unloading (tissues), reaction shifts to left (and H⁺ is incorporated into H₂O)

During CO₂ loading (lungs), reaction shifts to right (and H⁺ is buffered by proteins)

Does hypercapnia or acidosis cause more CO₂ to be removed from the blood?

Both (hypercapnia and acidosis) cause more CO₂ to be removed from the blood, pushing reaction to left, which reduces H⁺ concentration

Hypercapnia

P_CO2 in blood rises

Activates medullary chemoreceptors

Causes Increased respiratory rate and depth

Acidosis

Rising plasma H⁺ activates peripheral chemoreceptors

Causes increased respiratory rate and depth

Alkalosis

Depresses respiratory center

Respiratory rate and depth will decrease, causing H⁺ concentration to increase

Respiratory system impairment that causes acid-base imbalances

Hypoventilation causes respiratory acidosis

Hyperventilation causes respiratory alkalosis

Renal Regulation

Acid-base balance by adjusting amount of bicarbonate in blood by:

• Conserving (reabsorbing) or generating new HCO₃^-

• Excreting HCO₃^-

• Excreting H⁺

• Excreting NH₄⁺

Metabolic acidosis

Metabolic alkalosis

Metabolic acidosis

Low blood pH and HCO₃^-

Rising blood pH and HCO₃^-

Blood pH below 6.8

Causes depression of CNS, which can lead to coma and death

Blood pH above 7.8

Causes overexcitation of nervous system, leading to muscle tetany, extreme nervousness, convulsions, and death, often from respiratory arrest

Respiratory and Renal Compensations

If acid-base imbalance is due to malfunction of one physiological buffer system, other system tries to compensate

What does Respiratory system attempt to correct?

Metabolic acid-base imbalances

What does Kidneys attempt to correct?

Respiratory acid-base imbalances