Exam 4: Respiratory & Renal Flashcards
What is respiration (2 terms)
Mitochondrial O2 utilization (aerobic metabolism)
Ventilation
- breathing
- gases move via bulk flow
- conducting airways are essential
What is the thorax (chest wall, thoracic cavity, pleural cavity)
Chest wall
- diaphragm (skeletal)
- thorax: rib cage, spinal column, trunk muscles
Thoracic cavity
- lungs, trachea, heart, large vessels, esophagus, thymus
Pleural cavity
- space between visceral and parietal pleurae
Explain the conducting zone
Conducts air flow to respiratory zone
Warms and humidifies inspired air
Cleans air
- secretes mucus
- cilia move mucus
- where emphysema and cystic fibrosis can occur
Understand ciliated epithelium in the conducting zone
Watery saline layer allows cilia to push mucus toward pharynx
What is cystic fibrosis - lungs
Normal airway
- airway is usually lined with thin layer of mucus
CF airway
- thick, sticky mucus blocks the airway and they lack the watery layer which would normally allow cilia to push mucus toward pharynx
Conducting zone vs. Respiratory zone
Conducting zone
- 1 branch to many branches
- trachea -> bronchi -> bronchioles -> terminal bronchioles
Respiratory zone
- GAS EXCHANGE!
- respiratory bronchioles -> alveolar ducts -> alveolar sacs
- capillaries cover the alveoli
What is the site of gas exchange and explain how it works
Some alveolar walls have pores that allow air to flow between alveoli
Type I alveolar cells
- Alveoli walls are lined by a thin layer of water (continuous layer)
- Main site of gas exchange
Type II alveolar
- produce a detergent-like substance called surfactant (lowers surface tension of water); thin film of water
Explain alveoli
Primary site of gas exchange
About 300 million in adult lungs
- 1/2 tennis court surface area
- barrier to diffusion is 2 cells across so very quick
Alveolar cell types:
- type I: epithelial with structural function (80-90%) thin and interconnected by pores
- type II: secrete surfactant
- macrophages (clean debris through phagocytosis)
Explain the respiratory zone and the airway vs. cross-sectional area graph
Respiratory bronchioles among alveoli and alveoli with alveolar pores
Air moves via DIFFUSION
Define the different types of respiratory pressures
Intrapulmonary or alveolar pressure (Pa)
- equals atmospheric pressure at ‘rest’
- altered by changes in lung volume
Intrapleural pressure (Ppl)
- sub-atmospheric (negative) at rest
- determined by lungs and chest wall
- Ppl is always more negative than Pa
- Ppl is affected by forces of gravity
Transpulmonary pressure
- pressure difference across lungs (Pa - Ppl)
- determines lung volume
Patm - Pa = transairway pressure
Pa - Ppl = transpulmonary pressure
Understanding pressure change in lung using Boyle’s Law
P1V1 = P2V2
Ideal gas law: PV = nRT (a constant if temp and number of molecules is unchanged)
- if container shrinks (↓V, ↑P and vise versa; inversely proportional)
Changes in lung volume alter intrapulmonary pressure (Pa)
With lung expansion Pa falls below ATM pressure (Patm) - air flows in (↑V, ↓P)
With lung compression Pa increases above Patm - air flows out (↓V, ↑P)
Explain inspiration and how pressures change
Diaphragm contracts, ↑ thoracic volume
Parasternal/external intercostals contract, pulling the ribs up and out, ↑ V
Intrapleural pressure (Ppl) becomes more negative
Lungs open and ↑ lung volume
Intrapulmonary pressure (Pa) is more negative (subatmospheric)
Air flows into lungs
What are the muscles of inspiration and expiration
Inspiration:
- Sternocleidomastoid scalenes (activate when struggling to breathe)
- external and parasternal intercostals
- diaphragm
Passive expiration involves inspiration muscles to relax
Expiration (Active):
- internal intercostals
- external & internal abdominal oblique
- transverse abdominus
- rectus abdominus
Explain expiration and how pressures change
Passive (sleep, quiet breathing)
- inspiration muscles relax
- ↑ intrapleural pressure (Ppl)
- ↓ lung volume
- ↑ intrapulmonary pressure (Pa)
- air flows out of lungs
Active (exercise, speech, cough, panting, etc - forcing air out):
- Internal intercostal and abdominal muscles contract
- expiratory pressures ↑
- air flow faster
Explain pressure changes in quiet breathing with inspiration and expiration
Inspiration
- Pa < Patm (about 3 mmHg below)
Expiration
- Pa > Patm (about 3 mmHg above)
Explain pneumothorax and how it occurs
Collapsed lung
- air enters pleural space, which collapses the lung
- pleural pressure loses its negativity
- lung cannot hold shape and collapses
- decease transpulmonary pressure
Open
- air enters from chest wall
Closed
- air enters from lung injury (chest wall is intact)
Explain airway resistance
Lung resistance
- how easy air flows in airway
Pressure for air flow
- Flow = △Pressure/Resistance
Determined by airway diameter
- Smooth muscle tone (asthma)
- Support by surrounding tissue (emphysema)
- respiratory zone - held open by surrounding tissue
Explain compliance and pulmonary fibrosis
The ability to stretch
Change in lung volume per change in pulmonary pressure (Pa - Ppl)
- C = △V/△P
Lungs are very stretchy
Determined by lung structure and surface tension (lower means ↑ compliance)
Pulmonary fibrosis - stiff fibrous tissue that restricts lung inflation (i.e. black lung)
Total compliance includes both lung and chest wall compliance
How surface tension affects compliance
Alveoli lined by thin liquid layer
H2O molecules in liquid attract one another
This attraction generates tension at the air-liquid surface
Water tension within alveoli acts like a pressure pulling alveoli closed
More surface tension resists lung expansion
How surfactant affects compliance
Surfactant -> phospholipid mixture, which is in alveolar type II cells
Surfactant lowers surface tension of water, which increases compliance
More effective as alveolar radius decreases
Explain respiratory distress syndrome
In premature babies - type II alveoli cells are not mature enough to produce surfactant
Too little surfactant causes alveoli to collapse (having to reinflate every breath) which is a huge amount of work - ↓ Compliance
Usually a premature baby can have this bc surfactant is normally made in last 2 months of utero
- steroids may be given to stimulate production
- artificial surfactant is also available
Explain elastic recoil
Snap back
Result of elastic fibers in lung tissue
Lungs can recoil back to original shape
Compliance is different than elastic recoil
- A highly compliant lung does not mean it will return to resting volume after stretching force is released
Emphysema is a disease that destroys elastin fibers decreasing elastic recoil
Explain gas exchange in the lungs
Gases move between air and blood by diffusion due to [ ] gradient
- O2 diffuses from air to blood
- CO2 diffuses from blood to air
- this is rapid due to large surface area and short diffusion distance
- each gas moves down its [ ] or partial pressure gradient
Explain dalton’s law and partial pressure
Dalton’s law
- pressure of gas mixture = sum of pressures each gas exerts independently
PATM = PN2 + P02 + PC02 + PH20= 760 mm Hg
Partial pressure
- pressure exerted by one gas in a mixture
- dry air is 21% oxygen
- PO2 = 0.21 x 760 = 150 mm Hg
Explain gas partial pressures of inspired air vs alveolar air
Explain henry’s law with pressure equilibrate between air and blood
Gas dissolved in liquid exerts a pressure
In liquid equilibrated with a gas mixture, partial pressures are equal in the 2 phases
The amount of each gas dissolved in liquid is determined by
- temp in fluid
- partial pressure of the gas
- solubility of the gas
Explain RBCs
Flattened biconcave discs with a large surface area to promote diffusion of gases
Each RBC contains hemoglobin that contains iron
The iron group of the heme helps to transport O2 from the lungs to the tissues
Explain the oxyhemoglobin dissociation curve
S-Shape
- binding cooperatively
Upper plateau
- O2 loading in lungs
Steep slope
- unloading in tissues
As PO2 increases, % of hemoglobin saturated with bound oxygen increases until all of the binding sites are occupied at 100% saturation
Systemic venous blood is typically 75% saturated with oxygen
Explain changes in O2 binding in terms of pH and H+ changes
↑pH and ↓H+
- left shift (more affinity)
↓pH and ↑H+
- right shift (less affinity)
Explain changes in O2 binding in terms of PCO2 changes
↓PCO2
- left shift (more affinity)
↑PCO2
- right shift (less affinity)
Explain changes in O2 binding in terms of temperature changes
↓Temperature
- left shift (more affinity)
↑Temperature
- right shift (less affinity)
Explain changes in O2 binding in terms of DPG changes
↓ 2,3-DPG
- left shift (more affinity)
↑ 2,3-DPG
- right shift (less affinity)
Explain CO2 transport in blood and percentages
HCO3- (70%): Carbonic anhydrase
Dissolved CO2 (10%)
Carbaminohemoglobin (20%)
Explain CO2 uptake in periphery
Explain the O2 flow gradient
Explain CO2 release in lungs
Explain the CO2 flow gradient
Low concentration of carbon dioxide in the alveolar air sets up the gradient that moves it from the pulmonary blood into the alveolar air
At active cells, the production of carbon dioxide during fuel catabolism sets up the gradient to move it from the cells into the systemic blood
What are the types of ventilation and breathing patterns
What is alveolar ventilation and the associated pressures
Pathological conditions that reduce alveolar ventilation and gas exchange
PO2 normal in alveoli and blood
What is Emphysema and the associated pressures
Destructive disease
↓ alveoli ↓ surface area (↓ gas exchange; ↓ diffusion)
↓ elastic recoil of lung
↑ Lung compliance (very stretchy)
PO2 is normal/low in alveoli and PO2 low in the blood
What is Fibrotic lung disease and the associated pressures
Restrictive Disease
Thicker alveoli - ↑ distance for diffusion (slows gas exchange)
Loss of lung compliance
Ex: Black Lung (inhalation of particulate matter)
PO2 is normal/low in the alveoli and PO2 is low in the blood
What is Asthma and the associated pressures
Hypersensitivity of the smooth muscle tone
Obstructive disease
↑ Airway resistance, ↓ Ventilation
Bronchioles constricted, PO2 low in alveoli, and PO2 low in blood
Explain COPD and treatment
Emphysema (destructive) and chronic bronchitis (obstructive)
Treatment:
- Quit smoking, avoid lung irritants
- Medicines - bronchodilators, steroids, flu shots, oxygen therapy
- Surgery-bullectomy, lung volume reduction surgery (removing dead parts), lung transplant
Draw and label the spirometry graph
Tidal volume
- volume of gas inspired or expired in an unforced respiratory cycle
Inspiratory reserve volume
- maximum volume of gas that can be inspired during forced breathing
Expiratory reserve volume
- maximum volume of gas that can be expired during forced breathing
Residual volume
- volume of gas remaining in lungs after a maximum expiration
Total lung capacity
- total amount of gas in lungs after maximum inspiration
Vital capacity
- maximum amount of gas that can be expired after max inspiration
Inspiratory capacity
- max amount of gas that can be inspired after normal tidal expiration
Functional residual capacity
- gas remaining in lungs after a normal tidal expression
Explain the forced vital capacity with emphysema/COPD
During forced exhalation, uneven transmural pressures within the lungs can cause some airways to collapse
Air becomes trapped in these collapsed airways to reduce the forced vital capacity (FVC)
High volume of gas trapping will cause forced vital capacity (FVC) to be smaller
Explain the FEV1/FVC ratio and how it changes with disease
FEV -> forced expiratory volume in 1 sec
FVC -> forced vital capacity
Ratio is calculated in order to diagnose obstructive and restrictive lung disease
Changes with disease:
- Restrictive Disease: i.e. black lung; ratio is similar to normal ratio but less volume
- Obstructive disease: i.e. asthma; can reduce ratio by increasing resistance of air flow
- Severe Obstructive Disease: COPD; can increase resistance and decrease FVC due to gas trapping
What is pulmonary edema and the associated pressures
Excess interstitial fluid ↑ diffusion distance
I.e. congestive heart failure
PO2 in alveoli is normal, PO2 in blood is low
↑ Blood hydrostatic pressure
What is pneumonia?
An infection of one or both lungs, in which alveoli fill with pus and other liquid
Explain COVID-19; What other issues it can cause; How we can help it
Disease caused by the coronavirus, can cause lasting lung damage (fibrosis)
Can cause:
- Lung complications (pneumonia) and in severe cases ARDS (acute respiratory) -> Type II alveoli cells
- Fluid enters alveolus disrupting normal gas exchange
- Alveoli can collapse due to fluid and loss of surfactant
Treat with:
- vaccines, antivirals, ventilator, steroids (↓ inflammation), ECMO, proning (on stomach/side)
Explain obstructive sleep apnea
Explain what an oximeter is and how it works
Measures percentage of hemoglobin in the blood
Device sends 2 different wavelengths of light (red and infrared) through the finger and measuring the light with a photodetector as it exits
Hemoglobin absorbs light differently depending on its saturation with O2
Normally ranges 95-100, lower indicates hypoxemia or low blood oxygen
Explain pulmonary reflexes and ventilation and the receptor types
Receptor reflexes that affect automatic breathing
Sensory fibers in vagus
3 receptor types:
Unmyelinated C fibers
- respond to bradykinin, histamine (injury)
- produces rapid/shallow breathing (pain)
Rapidly-adapting receptors
- located in airway mucosa
- respond to inhaled irritants
- stimulate cough
Pulmonary stretch receptors (Hering breuer reflex
- Sense lung volume - expansion reduces inspiration effort (preventing over inflation of lungs)
- Important for normal breathing pattern in infants
How is ventilation measured
Rf = frequency (breaths/min)
Vt = tidal volume (ml)
Minute ventilation = Rf x Vt
-> Vd = atomic dead space (air in conducting zone)
-> Lungs are bidirectional, which means air can get trapped in the conducting zone
Alveolar ventilation = Rf x (Vt - Vd)
- Vd usually around 150ml
- strongly affects gas exchange
- slow, deep breathing vs. panting (cause change in alveolar ventilation without change in minute ventilation)
What is central hypoventilation syndrome
Loss of “automatic” respiratory pathway
Must be conscious (awake) to voluntarily control breathing
rare, but shows that there are 2 separate pathways -> voluntary and involuntary
Normal “automatic” breathing is generated in medulla -> respiratory rhythm generator (multiple groups of neurons signaling)
Explain the medullary respiratory centers
No respirator “pacemaker cells”
Neuron groups interact to generate basic inspiratory pattern
Neurons project to spinal motor neurons that innervate respiratory muscles
Explain the neural control of breathing and the pathway
At the PNS (always sensing PCO2 and pH) which is the aortic and carotid bodies
CNS is at the medulla oblongata
Explain how higher brain regions control breathing
Cerebral cortex
- conscious control (“hold your breath”)
- separate spinal pathway
Subcortical Regions
- automatic coordination
- motor tasks (“stop breathing when you thread a needle”)
- emotion (“stop breathing during last second shot of a game”)
Pons
- fine-tunes medullary output
- integrates vagus nerve input
Explain how PNS chemoreceptors work
Monitor changes in arterial blood PCO2, PO2, pH (mainly only PCO2 and pH on a breath by breath basis)
Peripheral (carotid bodies and aortic bodies and will detect PO2 if it drops dramatically)
Aortic bodies stimulated by:
- rise in arterial PCO2
- rise in arterial H+, fall in pH
- fall in arterial PO2 (**sensitive to this signal i.e. large drop)
- rapid response (sec)
Arterial PCO2 is primary variable regulated by automatic breathing
Explain how central chemoreceptors work
Detect changes in arterial PCO2- via pH
H+ does not cross blood-brain barrier
CO2 diffuses in, forms H2CO3 (carbonic acid)
Neurons detect drop in CSF pH
Slow response (min)
Explain how arterial PCO2 is controlled and the pathway
Controlled by negative feedback loop
Know the graphs showing how PCO2 and PO2 effect ventilation
Explain work and exercise
Work -> effort used to move a mass
W = Force x Distance
Exercise -> work at a faster rate
Work rate = work/time
Proportional to volume of CO2 produces (Vco2) and volume of O2 consumed (Vo2) per unit time
Direct indication of metabolic needs
Proportional to heart rate and minute ventilation (Ve)
Explain how increased cardiac output works in terms of supplying O2 to skeletal muscles and the paths
Explain the redistribution of blood flow during exercise (vasoconstriction vs vasodialation)
How does heart rate relate to exercise
Ventilation and heart rate increase with exercise
How does tidal volume and stroke volume compare with exercise
Tidal volume and stroke volume increase with exercise intensity but flatten out
Work of expanding increases (resistance and stretch) -> law of diminishing returns -> start to spend more O2 to get O2
Explain how exercise relates to transit time in pulmonary capillary
Exercise shortens transit time in pulmonary capillary but does not change PO2 pulmonary venous blood
Explain how blood gases remain relatively stable during exercise
Because ventilation is increasing to keep PO2 and PCO2 stable
At some point ventiliation can increase all the way to hyperventiliation, where PO2 has no change and PCO2 starts to drop
Explain how H+ concentration effects ventilation
Summarize the changes with exercise in terms of redistribution of blood flow, pulmonary blood flow, and changes in ventilation
What are the functions of the renal system
- Regulates water and electrolyte (Na+, K+, Cl-, Ca++, Mg++, PO4–) balance
- Excrete endogenous (urea) and exogenous (drug metabolites) waste products
- Regulate arterial blood pressure and RBC synthesis
- renin angiotensin aldosterone signaling (affect total peripheral resistance)
- erythropoietin (stimulates RBC production) - Regulates plasma pH (H+ and HCO3-)
HCO3- = bicarbonate
What is homeostasis in terms of water, electrolytes, & other things
Maintain overall fluid/electrolyte homeostasis
Note done solely by the kidneys but they are vital (other systems involved)
If kidneys are non-functioning, need dialysis every 2-3 days
What is the 60-40-20 rule
60% H2O
40% Intracellular H2O
20% extracellular H2O
Total body water (TBW) = 60% of body weight
TBW = ICF (intracellular) + ECF (extracellular)
ECF = plasma (1/4) + interstitial fluid (3/4)
Explain the regulation of water in the body
What are the organs of the urinary system
2 kidneys
Renal artery + vein
Ureter - smooth muscle
Bladder - smooth muscle, storage sac, normally sterile
Urethra
- smooth muscle (4cm female; 20cm male)
- site of potential UTI
- Internal urethral sphincter - smooth muscle
- innervated by automatic nerves (parasympathetic)
- external urethral sphincter (skeletal muscle - voluntary)
What is the structure of the kidney
Outer cortex: Contains many capillaries
Medulla: Pyramid contains minor calyces which unite to form a major calyx
Major calyces form renal pelvis, renal pelvis collects urine -> Transport urine to ureters
Explain renal vasculature
20-25% of cardiac output goes to the kidneys
Allows kidneys to constantly process extracellular fluid
Essential to allow enough oxygen to sustain function
How does blood flow in and out of the kidney
Renal artery -> interlobar artery -> arcuate artery -> interlobular artery -> portal arterial system -> interlobular vein -> arcuate vein -> interlobar vein -> renal vein
Explain the micturition reflex
Reflex control center in spinal cord regulates internal and external urethral sphincters
Filling of bladder activates stretch receptors that send impulses to the micturition center
- activates parasympathetic system causing contraction of detrusor muscle and inhibition of sympathetic causes relaxation of internal urethral sphincter
↑ stretch, ↑ parasymp activity, ↑ detrusor muscle contracts
↓ skeletal muscle neuron input, opens external sphincter
Urination occurs when descending motor tracts from micturition center inhibit somatic motor neurons to relax external urethral sphincter
Explain the nephron and what is needed for diffusion
Function unit of the kidney
Interface between blood and urine
Transport processes include diffusion and carrier-mediated transport
Needed for diffusion
- ↑ surface area, ↑ [ ] gradient, ↓ thickness
About 1 million nephrons per adult kidney
Each nephron is one epithelial cell thick
Proximal tube -> loop of henle -> distal tube -> collecting tube
Define excretion, filtered, secreted, reabsorbed
Excretion -> lost from body
Filtered -> moved from one compartment to another by selective diffusion (permeability)
Secreted -> transported out of blood into nephron
Reabsorbed -> transported out of nephron
Amount excreted = amount filtered + amount secreted - amount reabsorbed
Explain how glomerular filtration, tubular reabsorption, and tubular secretion works
Glomerular filtration: plasma filtered from glomerular capillaries into Bowman’s space
Tubular reabsorption: movement of substances from lumen into the peritubular capillary
Tubular secretion: movement of substances from the peritubular capillary into the lumen
What are the renal blood vessels
Afferent arteriole
- delivers blood into the glomeruli
Glomeruli (glomerular capillaries)
- capillary network that produces filtrate that enters urinary tubules/nephrons
Efferent arteriole
- delivers blood from glomeruli to peritubular capillaries
Peritubular capillaries (vasa recta)
- important for secretion and absorption
Explain the renal portal system
Portal system - 2 capillary beds in series
Afferent arteriole -> glomerular capillary -> efferent arteriole -> peritubular capillary
Allows blood to be altered and go immediately to next capillary bed
Glomerular capillaries - relatively high pressure
Peritubular capillaries - low pressure
Name and label the nephron tubules
glomerular capsule -> proximal convoluted tubule (PCT) -> descending and ascending limbs of loops of henle (LH) -> distal convoluted tubule (DCT) -> collecting duct (CD)
Function of the glomerular capsule and explain how it works
Filtration
Endothelial cells -> anchoring protein (basement membrane) -> epithelial cell lining (podocyte)
- filtration slits between these create a barrier of what can get into the nephron
Filtered:
- water, amino acids, glucose, electrolytes, <5000 daltons (molecular mass)
Not filtered:
- cells, proteins, fats, complex carbs, negatively charged molecules (can’t get through basement membrane), >5000 daltons
Ultrafiltrate:
- fluid that enters glomerular capsule
Glomerular filtration:
- producing ultrafiltrate under hydrostatic pressure of blood
Glomerular filtration rate (GFR):
- volume of filtrate produced by both kidneys each minute
- avg = 125ml/min
Explain how glomerular filtration rate (GFR) is increased or decreased
Explain the sympathetic regulation of GFR and the path
Stimulates vasoconstriction of afferent arterioles
- preserve blood volume to muscles and heart
- prevents rise in GFR with increased Cardiac Output (CO)
Explain auto-regulation of GFR
Ability of kidney to maintain a constant GFR despite systemic changes
– Achieved through effects of locally produced chemicals on the afferent arterioles
Maintaining GFR:
- When MAP drops to 70 mm Hg, afferent arteriole dilates
- When MAP increases, vasoconstrict afferent arterioles
Explain the function of the proximal convoluted tubule
REABSORPTION
- ↑ surface area & 2/3 of filtrate is absorbed
- reabsorbs salt and H2O
- returns back into peritubular capillaries
- keep the sugar save the glucose
About 180 L/day of ultrafiltrate produced but only 1-2L of urine excreted per day (only need 500ml/day urine needed to excrete metabolic wastes)
Made of Cuboidal epithelial cells and lots of microvilli
Explain paracellular vs transcellular
Transcellular:
- through cell membrane
- carriers (may be active, carrier-mediated)
- pores (passive)
Paracellular
- around cell (strictly passive diffusion & requires gradient)
Explain glucose and amino acid reabsorption in PCT
Filtered glucose and amino acids (small and filtered) are reabsorbed in PCT by secondary active transport with membrane carriers
Carrier mediated transport displays:
- saturation
- transported molecules concentration needed saturate carriers and achieve maximum transport rate
Renal transport threshold:
- minimum plasma [substance] that results in excretion of that substance in the urine
- renal plasma threshold for glucose = 180-200mg/dl
Explain electrolyte and water reabsorption in proximal tubule
PCT total [solute] = 300 mOsm/L
- same as plasma (ISOTONIC)
Reabsorption of H2O by osmosis
- cannot occur without active transport of Na+
Na+/K+ ATPase pump extrudes Na+
Electrical gradient causes Cl- movement towards higher [Na+]
H2O follows by osmosis
Explain the significance of PCT reabsorption
65% Na+, Cl-, H2O reabsorbed across the PCT into the vascular system
90% K+ reabsorbed
Reabsorption occurs constantly regardless of hydration state
- not subject to hormonal regulation
Energy expenditure is 6% of calories consumed at rest
What are the 2 types of nephrons and explain them
Cortical nephron (80% in human kidney)
- originates in outer 2/3 of cortex
- osmolarity of 300 mOsm/l
- involved in solute reabsorption
Juxtamedullary nephron (20% in human kidney)
- originates in inner 1/3 cortex
- important in the ability to produce a concentrated urine
- has longer loop of henle
Explain the descending limb of loop of henle
Deeper regions of medulla reach 1400 mOsm/L
Impermeable to passive diffusion of NaCl
Permeable to H2O
Hypertonic interstitial fluid causes H2O movement out of the descending limb via osmosis, and H2O enters capillaries
Fluid volume decreases in tubule, causing higher [Na+] in the ascending limb
Explain the ascending limb of the loop of henle
NaCl is actively extruded from the ascending limb into surrounding interstitial fluid
- NaCl is reabsorbed
Na+ diffuses into tubular cell with secondary active transport of K+ and Cl-
Occurs at a ration of Na+ : K+ : 2 Cl-
Impermeable to H2O
Explain the loop of henle in terms of osmolarity
It can generate an osmotic pressure of the medullary interstitial tissue fluid that can be 4x that of plasma (hyperosmotic)
This is due to descending being permeable to water and impermeable to NaCl which counters the ascending limb, which is impermeable to water and reabsorbed NaCl
Explain the peritubular capillaries (Vasa Recta)
Transports H2O from interstitial fluid
Recycles NaCl and urea
NaCl and urea diffuse into descending limb and diffuse back into medullary tissue fluid
At each level of the medulla [solute] is higher in ascending limb than in the interstitial fluid AND higher in interstitial fluid than in descending
Walls of the capillaries are permeable to H2O, NaCl, and urea
Water always moves in vesa recta (due to colloid osmotic pressure in vasa recta > interstitial fluid)
Know the osmolarity of different regions of the kidney (nephron(
300 -> 1400 -> 100 -> 300 -> 1400
Explain the distal convoluted tube (DCT) and the function
Has epithelial cells and few microvilli
Secretion and reabsorption
Terminates in cortical collecting duct
Creates a hypotonic filtrate, which permits hypotonic urine excretion (water loss)
Explain the Juxtaglomerular apparatus
TGF = tubuloglomerular feedback which is responsible for Na+ reabsorption
Granular cells within afferent arteriole secrete renin
- initiates the renin-angiotensin-aldosterone system
- negative feedback
Macula densa
- region where ascending limb is in contact with afferent arteriole
-inhibits renin secretion when [Na+] in blood ↑
Explain the collecting duct (cortical portion) and its function
Reabsorption of NaCl controlled by aldosterone (secreted by adrenal cortex)
Aldosterone secretion stimulated by angiotensin II (RAAS)
Reabsorption of the final [Na+] in cortical collecting duct (about 15% of which is filtered) is controlled by aldosterone
When RAAS is activated, all Na+ in DCT is reabsorbed
Aldosterone ↑ Na+ retention (absorption) in exchange for K+ secretion
Explain the negative feedback loop to decrease plasma [Na+]
↑ [Na+] in blood
- ↑ filtered load - more Na+ in tubule
- inhibits renin - less renin released
RAAS is inhibited
- less conversion of angiotensin -> AI by renin
- less conversion of AI -> Angiotensin II by ACE in lung
- less angiotensin II leads to ↓ aldosterone signaling, ↓ Na+ reabsorption, ↓ water reabsorption (more urine produced)
Until [Na+] in blood returns to set point levels
Explain the Na+, K+, and H+ relationship
Aldosterone stimulates Na+ reabsorption in DCT cortical CD and creates electrical gradient for K+ secretion
During acidosis, H+ is secreted at the expense of K+
Explain K+ secretion in nephron
90% filtered K+ reabsorbed in early part of the nephron (PCT)
Secretion of K+ occurs in cortical CD
Amount of K+ secreted depends on
- amount of Na+ delivered to the region
- amount of aldosterone secreted
As Na+ is reabsorbed, lumen of tubule becomes negatively charged, which drives secretion of K+ into tubule
Transport carriers for Na+ are separate from transporters for K+
Final [K+] concentration controlled in CD by aldosterone
- when aldosterone is absent, no K+ is excreted in urine
ONLY means by which K+ is secreted
Explain the medullary collecting duct and its function
Impermeable to high [NaCl] that surrounds it
- walls of CD are permeable to H2O
H2O is drawn out of CD by osmosis
- rate of osmotic movement is determined by # of aquaporins (water pores) in the cell membrane
Permeable to H2O - depends on presence of ADH
- when ADH binds to its membrane receptors on CD, acts via cAMP, stimulating fusion of vesicles with plasma membrane and incorporates water channels into plasma membrane
Reabsorption of H2O
Explain the role of ADH in the CD
ADH stimulates insertion of pre-existing aquaporin channels into the luminal membrane, ↑ cyclic AMP -> ↑ translocation of channel-containing vesicles to luminal membrane -> ↑ fusion and insertion (exocytosis) -> ↑ water permeability
Process is reversible ↓ ADH -> vesicle retrieval (endocytosis) -> ↓ water permeability
Explain how ADH is regulated
Regulated by:
hypothalamic osmoreceptors: ∆ POSM → ∆ ADH → ∆ H2O reabsorption
Explain the osmolarity of urine
ISO-osmotic urine (300 mOsm)
- lose water and salt proportionally (no changes is plasma osmolarity)
- occurs when you balance water and salt intake with water and salt loss
HYPER-osmotic urine ( >300 mOsm)
- lose more salt than water (retaining more H2O than salt and ↓ plasma osmolarity)
HYPO-osmotic urine ( <300 mOsm)
- lose more H2O than salt (retain more salt than water and ↑ plasma osmolarity)
What is clearance from plasma
Ability to remove molecules from plasma and excrete those molecules in urine
If GFR is completely cleared, substance is filtered but not reabsorbed (but water is!)
- substance filtered but also secreted and excreted
Volume of plasma from which a substance is completely removed in 1min by excretion in the urine
Renal plasma clearance with be > 125 ml/min
Explain transport processes and renal clearance (think inulin)
If a substance is not reabsorbed or secreted
- amount excreted = amount filtered
Inulin is an exogenous substance not reabsorbed or secreted
Quantity inulin excrete (mg/min) = V x Ui
- V = rate of urine formation (ml/min)
- Ui = inulin/substance concentration in urine (mg/ml)
Explain the measurement of GFR
Rate at which inulin is filtered by the glomeruli
Quantity filtered = GFR x Pi
- Pi = [inulin/substance] in plasma
Amount filtered = amount excreted
GFR x Pi = V x Ui (usually 125ml/min)
Explain clearance of inulin
Clinically we measure creatinine concentration to see how filtration is going in the kidneys
Explain secretion from peritubular capillaries
Secretion of substance from peritubular capillaries into interstitial fluid then transported into lumen of tubule and into urine
Allows kidneys to rapidly eliminate certain substances including potential toxins
Explain renal clearance to measure renal blood flow
Not all blood delivered to glomeruli is filtered in glomerular capsules
- most glomerular blood passes to different efferent arterioles
- 20% renal plasma flow filtered and substances are returned back to blood
Substances in unfiltered blood can be secreted and cleared into tubules by active transport (PAH)
- PAH can be used to measure renal plasma flow
PAH = Aminohippuric acid or para-aminohippuric acid
Explain renal plasma flow
filtration and secretion clear the molecules dissolved in plasma
- PAH clearance measures renal plasma flow
- averages 625 ml/min
To convert to total renal blood flow, the amount of blood occupied by Red Blood Cells (erythrocytes) must be PAH taken into account
Explain total renal blood flow
45% blood is RBCs (hematocrit)
55% plasma
Total renal blood flow = PAH clearance/0.55
Rough estimate = 625ml/min / 0.55 = 1.1-1.2 L/min
Explain importance of urea in the nephron
Filtered, reabsorbed and excreted
Urea contributes to total osmolarity of interstitial fluid
Ascending limb LH and medullary CD are permeable to urea
- medullary CD has urea transporters
Urea diffuses out medullary CD and into ascending limb LH
Explain the clearance of urea
Urea is filtered into glomerular capsule and reabsorbed into blood
Urea clearance is 75ml/min (whereas inulin is 125 ml/min)
- 40-60% of filtered urea is always reabsorbed
Passive process occurs via facilitated diffusion of ureas
> 125 filtered and secreted
< 125 filtered and reabsorbed
Explain renal acid-base regulation
Kidneys help regulate blood pH by excreting H+ and reabsorbing HCO3-
Most of H+ secretion occurs across the walls of the DCT in exchange for Na+
- antiport mechanism moves Na+ and H+ in opposite directions
Normally urine is slightly acidic because the kidneys reabsorb almost all HCO3- and excrete H+
- returns blood pH back to normal range
Explain the reabsorption of HCO3-
Apical membranes of tubule cells are
impermeable to HCO3-
– Reabsorption is indirect
When urine is acidic, HCO3- combines with H+ to form H2CO3, which is catalyzed by Carbonic anhydrase (ca) located in the apical cell membrane of PCT
– As [CO2] increases in the filtrate, CO2 diffuses into tubule cell and forms H2CO3
– H2CO3 dissociates to HCO3- and H+
HCO3- generated within tubule cell diffuses into peritubular capillary
Explain the acidification of urine
In states of acidosis the kidney must excrete more H+
This occurs in the distal tubule … the secreted H+ combines with two lumen buffers … phosphate and NH3
Explain urinary buffers
Nephron cannot produce a urine pH < 4.5
In order to excrete more H+, the acid
must be buffered
H+ secreted into the urine tubule and combines with HPO4-2 or NH3
Explain the regulation of blood pH
Respiratory acidosis - hypoventilation
- ↑ CO2 -> ↑ H+
Respiratory alkalosis - hyperventilation
- to treat, we would give a medication causing metabolic acidosis
Metabolic acidosis - Loss of HCO3-
Metabolic alkalosis - Loss of H+
Initial disturbance and compensation
- resp. acidosis leads to compensating metabolic alkalosis
Name the diuretics and explain how they work
They ↑ urine volume excreted
- ↑ the proportion of glomerular filtrate that is excreted as urine
Loop diuretics
- inhibit NaCl transport out of the ascending limb LH
Thiazide diuretics
- inhibit NaCl reabsorption in the 1st segment of DCT
Osmotic diuretics
- ↑ osmotic pressure of filtrate (mannitol)
Carbonic anhydrase inhibitors
- inhibits reabsorption of HCO3- in PT
Potassium sparing
- inhibits actions of aldosterone or Na+ reabsorption/K+ secretion in the DT/CD
Explain impaired renal function
- Water and electrolyte imbalance
- change body fluid volume, osmolarity, electrolyte imbalance including hyperkalemia (high extracellular K+) - Uremic toxicity (azotemia ↑ plasma creatinine and blood urea nitrogen levels)
- Changes in blood pressure, edema (plasma protein imbalance) and anemia (decreased erythropoietin synthesis)
- due to fluid imbalance
- erythropoietin stimulates RBC production - Metabolic acidosis (pH < 7.4)
- not secreting ions like needed
Name and explain kidney diseases; Percentage of those with kidney disease
10% of U.S. adults have some form of kidney disease
Acute renal failure (reversible)
- Pre-ARF ↓ renal blood flow and GFR
- Intro- ARF tubular necrosis (ischemic, toxin)
- Post-renal ARF urinary tract obstruction
Chronic renal failure
- Glomerulonephritis, hypertension, diabetes
End-stage renal disease
- GFR < 10%
- renal transplant (limited supply, rejection)
- dialysis (uses diffusion across artificial membrane (hemo-) or capillaries (peritoneal))
Explain hemodialysis
Blood flows through the upper compartment (recirculate)
Dialysis fluid flows in the counter direction through the lower compartment (frequent renewed)
- Renal failure -> ↑ plasma creatinine, hyperkalemia (↑[K+] ), ↑ water
- low concentration in the dialysis fluid, allows net diffusion from blood into dialysate
- Excess water is removed by hydrostatic pressure (high in blood, low in dialysate)
- 3-5 hr treatment period, repeated every 2-3 days
