Exam 4: Respiratory & Renal Flashcards

1
Q

What is respiration (2 terms)

A

Mitochondrial O2 utilization (aerobic metabolism)

Ventilation
- breathing
- gases move via bulk flow
- conducting airways are essential

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2
Q

What is the thorax (chest wall, thoracic cavity, pleural cavity)

A

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

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3
Q

Explain the conducting zone

A

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

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4
Q

Understand ciliated epithelium in the conducting zone

A

Watery saline layer allows cilia to push mucus toward pharynx

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5
Q

What is cystic fibrosis - lungs

A

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

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6
Q

Conducting zone vs. Respiratory zone

A

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

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7
Q

What is the site of gas exchange and explain how it works

A

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

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8
Q

Explain alveoli

A

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)

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9
Q

Explain the respiratory zone and the airway vs. cross-sectional area graph

A

Respiratory bronchioles among alveoli and alveoli with alveolar pores

Air moves via DIFFUSION

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10
Q

Define the different types of respiratory pressures

A

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

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11
Q

Understanding pressure change in lung using Boyle’s Law

A

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)

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12
Q

Explain inspiration and how pressures change

A

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

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13
Q

What are the muscles of inspiration and expiration

A

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

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14
Q

Explain expiration and how pressures change

A

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

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15
Q

Explain pressure changes in quiet breathing with inspiration and expiration

A

Inspiration
- Pa < Patm (about 3 mmHg below)

Expiration
- Pa > Patm (about 3 mmHg above)

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16
Q

Explain pneumothorax and how it occurs

A

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)

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17
Q

Explain airway resistance

A

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

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18
Q

Explain compliance and pulmonary fibrosis

A

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

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19
Q

How surface tension affects compliance

A

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

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20
Q

How surfactant affects compliance

A

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

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21
Q

Explain respiratory distress syndrome

A

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

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22
Q

Explain elastic recoil

A

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

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23
Q

Explain gas exchange in the lungs

A

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

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24
Q

Explain dalton’s law and partial pressure

A

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

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25
Q

Explain gas partial pressures of inspired air vs alveolar air

A
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26
Q

Explain henry’s law with pressure equilibrate between air and blood

A

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

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27
Q

Explain RBCs

A

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

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28
Q

Explain the oxyhemoglobin dissociation curve

A

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

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29
Q

Explain changes in O2 binding in terms of pH and H+ changes

A

↑pH and ↓H+
- left shift (more affinity)

↓pH and ↑H+
- right shift (less affinity)

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30
Q

Explain changes in O2 binding in terms of PCO2 changes

A

↓PCO2
- left shift (more affinity)

↑PCO2
- right shift (less affinity)

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31
Q

Explain changes in O2 binding in terms of temperature changes

A

↓Temperature
- left shift (more affinity)

↑Temperature
- right shift (less affinity)

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32
Q

Explain changes in O2 binding in terms of DPG changes

A

↓ 2,3-DPG
- left shift (more affinity)

↑ 2,3-DPG
- right shift (less affinity)

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33
Q

Explain CO2 transport in blood and percentages

A

HCO3- (70%): Carbonic anhydrase

Dissolved CO2 (10%)

Carbaminohemoglobin (20%)

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34
Q

Explain CO2 uptake in periphery

A
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35
Q

Explain the O2 flow gradient

A
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36
Q

Explain CO2 release in lungs

A
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37
Q

Explain the CO2 flow gradient

A

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

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38
Q

What are the types of ventilation and breathing patterns

A
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39
Q

What is alveolar ventilation and the associated pressures

A

Pathological conditions that reduce alveolar ventilation and gas exchange

PO2 normal in alveoli and blood

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40
Q

What is Emphysema and the associated pressures

A

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

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41
Q

What is Fibrotic lung disease and the associated pressures

A

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

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42
Q

What is Asthma and the associated pressures

A

Hypersensitivity of the smooth muscle tone

Obstructive disease

↑ Airway resistance, ↓ Ventilation

Bronchioles constricted, PO2 low in alveoli, and PO2 low in blood

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43
Q

Explain COPD and treatment

A

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

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44
Q

Draw and label the spirometry graph

A

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

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45
Q

Explain the forced vital capacity with emphysema/COPD

A

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

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46
Q

Explain the FEV1/FVC ratio and how it changes with disease

A

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

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47
Q

What is pulmonary edema and the associated pressures

A

Excess interstitial fluid ↑ diffusion distance

I.e. congestive heart failure

PO2 in alveoli is normal, PO2 in blood is low

↑ Blood hydrostatic pressure

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48
Q

What is pneumonia?

A

An infection of one or both lungs, in which alveoli fill with pus and other liquid

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49
Q

Explain COVID-19; What other issues it can cause; How we can help it

A

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)

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50
Q

Explain obstructive sleep apnea

A
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51
Q

Explain what an oximeter is and how it works

A

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

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52
Q

Explain pulmonary reflexes and ventilation and the receptor types

A

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

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53
Q

How is ventilation measured

A

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)

54
Q

What is central hypoventilation syndrome

A

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)

55
Q

Explain the medullary respiratory centers

A

No respirator “pacemaker cells”

Neuron groups interact to generate basic inspiratory pattern

Neurons project to spinal motor neurons that innervate respiratory muscles

56
Q

Explain the neural control of breathing and the pathway

A

At the PNS (always sensing PCO2 and pH) which is the aortic and carotid bodies

CNS is at the medulla oblongata

57
Q

Explain how higher brain regions control breathing

A

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

58
Q

Explain how PNS chemoreceptors work

A

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

59
Q

Explain how central chemoreceptors work

A

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)

60
Q

Explain how arterial PCO2 is controlled and the pathway

A

Controlled by negative feedback loop

61
Q

Know the graphs showing how PCO2 and PO2 effect ventilation

A
62
Q

Explain work and exercise

A

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)

63
Q

Explain how increased cardiac output works in terms of supplying O2 to skeletal muscles and the paths

A
64
Q

Explain the redistribution of blood flow during exercise (vasoconstriction vs vasodialation)

A
65
Q

How does heart rate relate to exercise

A

Ventilation and heart rate increase with exercise

66
Q

How does tidal volume and stroke volume compare with exercise

A

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

67
Q

Explain how exercise relates to transit time in pulmonary capillary

A

Exercise shortens transit time in pulmonary capillary but does not change PO2 pulmonary venous blood

68
Q

Explain how blood gases remain relatively stable during exercise

A

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

69
Q

Explain how H+ concentration effects ventilation

A
70
Q

Summarize the changes with exercise in terms of redistribution of blood flow, pulmonary blood flow, and changes in ventilation

A
71
Q

What are the functions of the renal system

A
  1. Regulates water and electrolyte (Na+, K+, Cl-, Ca++, Mg++, PO4–) balance
  2. Excrete endogenous (urea) and exogenous (drug metabolites) waste products
  3. Regulate arterial blood pressure and RBC synthesis
    - renin angiotensin aldosterone signaling (affect total peripheral resistance)
    - erythropoietin (stimulates RBC production)
  4. Regulates plasma pH (H+ and HCO3-)
    HCO3- = bicarbonate
72
Q

What is homeostasis in terms of water, electrolytes, & other things

A

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

73
Q

What is the 60-40-20 rule

A

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)

74
Q

Explain the regulation of water in the body

A
75
Q

What are the organs of the urinary system

A

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)

76
Q

What is the structure of the kidney

A

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

77
Q

Explain renal vasculature

A

20-25% of cardiac output goes to the kidneys

Allows kidneys to constantly process extracellular fluid

Essential to allow enough oxygen to sustain function

78
Q

How does blood flow in and out of the kidney

A

Renal artery -> interlobar artery -> arcuate artery -> interlobular artery -> portal arterial system -> interlobular vein -> arcuate vein -> interlobar vein -> renal vein

79
Q

Explain the micturition reflex

A

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

80
Q

Explain the nephron and what is needed for diffusion

A

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

81
Q

Define excretion, filtered, secreted, reabsorbed

A

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

82
Q

Explain how glomerular filtration, tubular reabsorption, and tubular secretion works

A

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

83
Q

What are the renal blood vessels

A

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

84
Q

Explain the renal portal system

A

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

85
Q

Name and label the nephron tubules

A

glomerular capsule -> proximal convoluted tubule (PCT) -> descending and ascending limbs of loops of henle (LH) -> distal convoluted tubule (DCT) -> collecting duct (CD)

86
Q

Function of the glomerular capsule and explain how it works

A

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

87
Q

Explain how glomerular filtration rate (GFR) is increased or decreased

A
88
Q

Explain the sympathetic regulation of GFR and the path

A

Stimulates vasoconstriction of afferent arterioles
- preserve blood volume to muscles and heart
- prevents rise in GFR with increased Cardiac Output (CO)

89
Q

Explain auto-regulation of GFR

A

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

90
Q

Explain the function of the proximal convoluted tubule

A

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

91
Q

Explain paracellular vs transcellular

A

Transcellular:
- through cell membrane
- carriers (may be active, carrier-mediated)
- pores (passive)

Paracellular
- around cell (strictly passive diffusion & requires gradient)

92
Q

Explain glucose and amino acid reabsorption in PCT

A

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

93
Q

Explain electrolyte and water reabsorption in proximal tubule

A

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

94
Q

Explain the significance of PCT reabsorption

A

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

95
Q

What are the 2 types of nephrons and explain them

A

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

96
Q

Explain the descending limb of loop of henle

A

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

97
Q

Explain the ascending limb of the loop of henle

A

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

98
Q

Explain the loop of henle in terms of osmolarity

A

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

99
Q

Explain the peritubular capillaries (Vasa Recta)

A

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)

100
Q

Know the osmolarity of different regions of the kidney (nephron(

A

300 -> 1400 -> 100 -> 300 -> 1400

101
Q

Explain the distal convoluted tube (DCT) and the function

A

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)

102
Q

Explain the Juxtaglomerular apparatus

A

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 ↑

103
Q

Explain the collecting duct (cortical portion) and its function

A

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

104
Q

Explain the negative feedback loop to decrease plasma [Na+]

A

↑ [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

105
Q

Explain the Na+, K+, and H+ relationship

A

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+

106
Q

Explain K+ secretion in nephron

A

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

107
Q

Explain the medullary collecting duct and its function

A

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

108
Q

Explain the role of ADH in the CD

A

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

109
Q

Explain how ADH is regulated

A

Regulated by:
hypothalamic osmoreceptors: ∆ POSM → ∆ ADH → ∆ H2O reabsorption

110
Q

Explain the osmolarity of urine

A

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)

111
Q

What is clearance from plasma

A

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

112
Q

Explain transport processes and renal clearance (think inulin)

A

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)

113
Q

Explain the measurement of GFR

A

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)

114
Q

Explain clearance of inulin

A

Clinically we measure creatinine concentration to see how filtration is going in the kidneys

115
Q

Explain secretion from peritubular capillaries

A

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

116
Q

Explain renal clearance to measure renal blood flow

A

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

117
Q

Explain renal plasma flow

A

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

118
Q

Explain total renal blood flow

A

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

119
Q

Explain importance of urea in the nephron

A

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

120
Q

Explain the clearance of urea

A

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

121
Q

Explain renal acid-base regulation

A

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

122
Q

Explain the reabsorption of HCO3-

A

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

123
Q

Explain the acidification of urine

A

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

124
Q

Explain urinary buffers

A

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

125
Q

Explain the regulation of blood pH

A

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

126
Q

Name the diuretics and explain how they work

A

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

127
Q

Explain impaired renal function

A
  1. Water and electrolyte imbalance
    - change body fluid volume, osmolarity, electrolyte imbalance including hyperkalemia (high extracellular K+)
  2. Uremic toxicity (azotemia ↑ plasma creatinine and blood urea nitrogen levels)
  3. Changes in blood pressure, edema (plasma protein imbalance) and anemia (decreased erythropoietin synthesis)
    - due to fluid imbalance
    - erythropoietin stimulates RBC production
  4. Metabolic acidosis (pH < 7.4)
    - not secreting ions like needed
128
Q

Name and explain kidney diseases; Percentage of those with kidney disease

A

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))

129
Q

Explain hemodialysis

A

Blood flows through the upper compartment (recirculate)

Dialysis fluid flows in the counter direction through the lower compartment (frequent renewed)

  1. Renal failure -> ↑ plasma creatinine, hyperkalemia (↑[K+] ), ↑ water
  2. low concentration in the dialysis fluid, allows net diffusion from blood into dialysate
  3. Excess water is removed by hydrostatic pressure (high in blood, low in dialysate)
  4. 3-5 hr treatment period, repeated every 2-3 days
130
Q
A