HPHY 325 Lecture Content: Comprehensive Review from Midterm II to Final Exam

What are the 2 main ions of secretion?

K+ and H+

Where is H+ secreted?

- PCT

- DCT

- Collecting duct

Purpose of H+ secretion

- pH balance

- H+ secretion is proportional to ECF acidity

Where and HOW is almost all filtered K+ reabsorbed?

- Proximal convoluted tubule

- PASSIVE diffusion via the PARACELLULAR route (low K+ in interstitial fluid due to pump)

Secretion of K+ in the DCT and Collecting duct

- Controlled by aldosterone

- Keeps blood K+ level constant

Why is plasma K+ kept within a normal range?

It affects resting membrane potential of cells

K+ reabsorption in the PCT (channel type, driving force, etc.)

- PASSIVE via concentration gradient made by Na+/K+ pump

- K+ concentration is HIGH inside of tubule cell

- K+ flows OUT of tubule cell via leak channels

K+ secretion in the DCT and collecting duct (channel type, driving force, etc.)

- K+ flows passively from peritubular capillaries into the interstitial fluid

- K+ is transported ACTIVELY from the interstitial fluid into the tubular cells (Na+/K+ pump)

- K+ leaves the tubule cell and goes into the DCT via passive flow through K+ leak channels (high concentration INSIDE cell)

What does aldosterone cause in order to increase K+ secretion?

- Increases Na+/K+ pumps in the basolateral membrane of tubule cells

- More K+ INTO cells from INTERSTITIAL FLUID

- More K+ flows OUT and into the lumen of the DCT/collecting duct with concentration

Water intake = ?

Water output

Intake of water

- 10% metabolism (ETC in mitochondria)

- 30% food

- 60% drinks

Output of water

- 10% feces

- 30% sweat

- 28% skin/lungs

- 60% urine

Osmolarity

- Number of solute particles in solution

- Osm/L (or Osm/kg for osmolality)

True or false: the osmolarity of filtrate changes as it moves through the renal tubule

True

True or false: filtrate in the glomerular capsule is iso osmotic to blood

True

What happens to osmolarity in the descending limb of the loop of Henle?

INCREASES

What happens to osmolarity in the ascending limb of the loop of Henle?

DECREASES

2 factors that impact our ability to concentrate our urine

1. Medullary osmotic gradient

2. Antidiuretic hormone (ADH)

What CREATES the medullary osmotic gradient?

Nephron loop

How does the nephron loop create the medullary osmotic gradient (just the term)?

Countercurrent multiplication

What PRESERVES the medullary osmotic gradient?

Vasa recta

How do the vasa recta preserve the medullary osmotic gradient (just term)?

Countercurrent exchange

What USES the gradient to adjust urine concentration?

- ADH

- Collecting duct

What type of nephrons establish medullary osmotic gradient?

Juxtamedullary nephrons

Out of water and Na+, what is the descending limb permeable to?

Water

Countercurrent flow

Fluid flows in opposite directions in the loop of Henle

3 properties of the nephron loop that ESTABLISH the medullary osmotic gradient

1. Countercurrent flow

2. H2O permeable in descending limb but no Na+ permeability

3. NaCl ACTIVELY pumped into interstitial fluid in the ASCENDING limb but no water permeability

What is the osmolarity difference between the ASCENDING limb and the interstitial fluid?

200 Osm/L

4 steps of countercurrent multiplication

1. NaCl actively pumped out of ASCENDING limb, causing increasing concentration in interstitial fluid

2. H2O pulled out of DESCENDING limb (osmosis)

3. Concentration of NaCl in DESCENDING limb is now HIGH

4. High concentration in descending limb then allows MORE NaCl to be pumped out of ASCENDING limb, creating even larger gradient with high concentration at the bottom of the loop

How many Osms of Na+ can Na+ pumps pump out at any given time?

200

Is the filtrate that enters the DCT after the nephron loop hypertonic or hypotonic or isotonic? Why is this important?

- HYPOtonic

- Means our urine is now more DILUTE than bodily fluids

ADH other name

Vasopressin

High ADH in the blood will result in urine that appears

DARK (concentrated)

What is the only thing ADH affects?

WATER reabsorption

What does ADH do and where does it act specifically?

- Allows us to reabsorb water in the DCT and collecting duct (usually no AQP-2 channels present!)

- Because the medullary osmotic gradient allows us to excrete dilute urine, ADH then allows water to flow out of the DCT where the filtrate is hypotonic, which then results in the filtrate becoming hypertonic (concentrated)

True or false: blood OSMOLARITY is the main control of ADH

True

ADH signal transduction

1. ADH binds to tubule target cells in the DCT and COLLECTING DUCT

2. Stimulates insertion of AQP-2 channels in the LUMINAL membrane (lumen of tubule)

3. Does this by using a cAMP 2nd messenger system

4. Water from tubule enters tubule cells because of the medullary osmotic gradient (hypotonic in DCT)

5. Water LEAVES via permanent AQP-3/4 channels in the BASOLATERAL membrane

6. More water in the interstitial fluids leads to more reabsorption by peritubular capillaries (osmosis)

Is ADH water soluble?

Yes

Why does alcohol make us dehydrated?

Alcohol inhibits the release of ADH

Overhydration response

1. Osmoreceptors in hypothalamus detect decreased osmolarity

2. ADH release is STOPPED from posterior pituitary

3. DCT and collecting duct become IMPERMEABLE to water

4. Urine becomes more dilute

In the DCT and collecting duct, when ADH is present, how does the amount of water pulled out into the interstitial fluid via AQP-2 channels change as you move down the collecting duct?

INCREASES as you move down because of increasing interstitial fluid osmolarity (deeper = more concentrated interstitial fluid)

Vasa recta

- "Straight vessels"

- Type of peritubular capillary

- Surrounds nephron loops of ONLY juxtamedullary nephrons

What must happen in the vasa recta, as they move down into the medulla, in order for the blood to be iso-osmotic to the interstitial fluid?

- Lose water

- Gain NaCl

Vasa recta function

1. Blood supply to renal medulla

2. Countercurrent exchange to maintain medullary osmotic gradient

How do vasa recta not distort the medullary gradient in the interstitial fluid?

- HIGH permeability to salt and water

- SLOW flow

- Iso-osmotic to interstitial fluid (more concentrated as it goes down)

- COUNTERCURRENT EXCHANGE

Countercurrent exchange definition

Exchange solutes and nutrients to maintain gradient in renal medulla

True or false: BOTH limbs of vasa recta are permeable to water AND NaCl

True

2 ways to determine renal function

1. Renal clearance

2. Urinalysis

Criteria for chronic renal disease

GFR <60 mL/min for 3 months or longer

What is chronic renal disease caused by?

- Diabetes mellitus (increased blood glucose causes damage to capillaries in glomerulus)

- Hypertension (damage to glomerular capillaries)

Renal clearance definition

The VOLUME (mL) of plasma that is cleared of a certain substance per 1 minute

Explain the phrase RC = 150 mL/min

In one minute, the kidneys have cleared all the substance present in 150 mL of plasma

GFR and renal clearance units

mL/min

What does it mean if something is ONLY filtered?

It is completely excreted in urine and completely filtered out of plasma

Inulin clearance

- 125 mL/min

- Equals GFR

- 0% reabsorbed

- DON'T make inulin must take it

Creatinine clearance

- 140 mL/min

- HIGHER than GFR

- DO make it so easy to use

How is creatinine formed?

Constantly produced by muscles as a waste product

Why is creatinine's GFR 140?

Because it is filtered but also secreted

Urea GFR

- 62.5 mL/min

- 50% of urea is REABSORBED per 125 mL of filtrate

- PASSIVE reabsorption

- RC < GFR

- 50% is EXCRETED

If something is filtered AND reabsorbed, what is the renal clearance in comparison to GFR?

LESS than GFR

Glucose renal clearance

- 0 mL/min

- ALL reabsorbed (normally)

- NO excretion unless one has diabetes mellitus

Urine composition (lots of stuff, just memorize it)

1. Solutes

- Nitrogenous wastes (urea, uric acid, creatinine)

- Sodium (Na+)

- Potassium (K+)

- H+

- Phosphates

- Sulfates

- TRACE bicarbonate

- TRACE Ca2+

- TRACE Mg2+

2. Water

% of composition of urine (water vs. solutes)

Normally, it is 5% solutes and 95% water

What should NEVER be in urine?

- All blood cells

- Protein

- Glucose

- Platelets

Glucose in urine (name and cause)

1. Glycosuria

2. Diabetes mellitus

Protein in urine (name and cause)

1. Proteinuria or albuminuria

2. Severe hypertension --> glomerulus damage allows for proteins to get through

Ketone bodies in urine (name and cause)

1. Ketonuria

2. Untreated diabetes mellitus OR starvation

Bile pigments in urine (name and cause)

1. Bilirubinuria

2. Liver disease OR obstruction of bile ducts

Erythrocytes in urine (name and cause)

1. Hematuria

2. Bleeding urinary tract via trauma, UTI or kidney stones

(Erythrocytes enter urine PAST nephron)

Leukocytes in urine (name and cause)

1. Pyuria

2. Pus due to a UTI (enters PAST the filtration sites)

Similarities between stomach and bladder

1. Rugae (folds of mucosa)

2. Visceral smooth muscle (STRESS-RELAXATION RESPONSE, OPTIMAL LENGTH OF MUSCLE BEYOND RESTING)

3. Three layers of muscle

3 layers of muscle in bladder

1. Inner longitudinal

2. Middle circular

3. Outer longitudinal

Bladder muscle name

Detrusor muscle

Bladder rugae

Allow STRETCH and storage

Internal urethral sphincter

- Thickening of detrusor muscle at the BLADDER/URETHRAL junction

- SMOOTH MUSCLE (involuntary - autonomic control)

External urethral sphincter

- Encircles urethra more DISTALLY from bladder

- Penis = distal to prostate

- Vagina = bottom portion of where bladder forms a "tube"

- SKELETAL MUSCLE (somatic control)

Micturition reflex

1. Stretch receptors in bladder activated

2. Visceral afferents sent to sacral spinal cord where they synapse with visceral afferents to the pons and PNS efferents

3. Visceral efferents (parasympathetic efferents) from spinal cord that also synapse with stretch receptors cause detrusor muscle to contract and the internal sphincter to RELAX

4. Pons sends information to cortex at the same time

5. Cortex (voluntary) decides whether to contract or relax external sphincter

Where is the micturition reflex center?

Pons

Mitosis

- Daughter cells are IDENTICAL to parent cell

- DIPLOID

- Growth and development

- 2 daughter cells

Meiosis

- Daughter cells are HAPLOID

- Sex cell production

- Cross combination

- NOT identical

- 4 daughter cells from one parent cell

Spermatogenic cells

- Develop into sperm

- START as UNDIFFERENTIATED stem cells at periphery of tubule

- Develop into sperm further into the lumen

Sertoli cells

- Sustenocytes

- Support spermatogenesis

- STIMULATION causes spermatogenesis

- Blood-testes barrier

- Energy source for sperm

- Phagocytic

- Secrete seminiferous fluid

- Secrete androgen binding proteins

- Secrete AMH during development (fetal)

Pathway of spermatogenesis with cells

1. Spermatogonia - 2N (stem cell, undifferentiated, periphery)

2. Mitosis yields 2 primary spermatocytes 2N (only one moves on, other remains as spermatogonia!)

3. Meiosis I yields 2 secondary spermatocyte (N)

4. Meiosis II yields 4 spermatids (N)

5. Spermiogenesis turns spermatids into spermatozoa (N)

How long does spermatogenesis take?

64 days

Hypothalamic-pituitary-gonadal axis (XX individual)

- HPG axis

- Estrogen, progesterone and inhibin inhibit anterior pituitary and hypothalamus

HPG axis (XY individual)

Testosterone and inhibin inhibit anterior pituitary and hypothalamus

Male sex hormone production

- Sustenacular cells (Sertoli cells) produce INHIBIN

- Sertoli cells produce ANDROGEN-BINDING protein (not a hormone but binds hormone)

- Interstitial Leydig cells produce TESTOSTERONE

Why doesn't synthetic testosterone increase spermatogenesis?

Because synthetic testosterone is only in the blood, and the blood-testes barrier prevents entrance into the tubule. ONLY LOCAL testosterone made by Leydig cells can enter

What effect does synthetic testosterone have?

- Decreased LOCAL testosterone (because inhibition of LH release which usually stimulates Leydig cells)

- Decreased sperm count

- Increased blood testosterone

Regulation of spermatogenesis

1. Neurotransmitter kisspeptin from Kiss1 neurons stimulates release of GnRH from hypothalamus

2. GnRH stimulates release of FSH and LH from anterior pituitary

3. LH stimulates Leydig cells to secrete testosterone

4. FSH AND TESTOSTERONE stimulate Sertoli cell activity (increased spermatogenesis)

5. Testosterone inhibits (- feedback) Kiss1 neurons AND release of LH from anterior pituitary

6. Sertoli cells release inhibin --> inhibition of anterior pituitary specifically for FSH (less secretion)

Testosterone stimulation and feedback

- INHIBITS Kiss1 neurons in hypothalamus causing general decrease in FSH and LH release

- SPECIFICALLY also inhibits LH release from anterior pituitary

- STIMULATES Sertoli cells to increase spermatogenesis

What does inhibin ALWAYS do?

Inhibits release of FSH from anterior pituitary (ONLY!)

Spermatogenesis vs. Oogenesis

- Chromosome replication and division are similar

- AMOUNT of CYTOPLASM that the final gametes receive is different

- TIMELINE for gamete production is very different

How long does oogenesis take?

11-50 years

How many sperm are made from one spermatogonia?

4

How many ovum are produced from one primary oocyte?

1

What happens to other other "ovum" besides ONE when meiosis II completes during oogenesis?

Other 3 get degraded (apoptosis)

How many primary oocytes are produced from 1 oogonium?

8

When does oogenesis start?

Before birth

When does meiosis I start on oogenesis?

7 months into development of fetus