Respiratory, Renal and Reproductive systems

• External respiration involves four key processes:

  • Exchange: atmospheric air to lung / alveoli
  • Exchange: alveoli to blood
  • Pulmonary and systemic circulation
  • Exchange: blood to cells
• External respiration involves:

  • Upper respiratory system: nasal cavity (primary entrance), mouth (secondary entrance), pharynx (throat), larynx, vocal cords,
  • Lower respiratory system: trachea, bronchi, bronchioles, alveoli and diaphragm
• Air flow is proportional to change in pressure and inversely proportional to resistance (dictated by airway diameter)
• Three important respiratory pressures includes:

  • Atmospheric pressure
  • Intra-alveolar pressure
  • Intrapleural pressure
• The transmural pressure gradient (difference in pressure between intrapleural and intra-alveolar pressures) prevents lungs from collapsing. This is because the intra-alveolar pressure is greater than the intrapleural pressure
• During inspiration, the diaphragm and external intercostal muscles both contract, expanding the volume of the thoracic cavity, expanding the lungs due to the strong hydrogen bonding in the pleura, decreasing the pressure in the lungs (both intra-alveolar and intrapleural). When this is less than atmospheric pressure, the pressure gradient moves air in.

  During expiration, the diaphragm and external intercostal muscles both relax, decreasing the volume of the thoracic cavity, causing pressure in lungs to increase and exceed atmospheric pressure
• The diameter of the conducting airways is regulated by the autonomic nervous system:

  • Parasympathetic nervous system: rest and digest -> slower ventilation rate -> decrease in air flow -> increase in resistance -> bronchorestriction
  • Sympathetic nervous system: fight or flight -> increase ventilation rate -> increase air flow -> decrease resistance -> bronchodilation
• Three factors contributing to the lungs ability to return into original shape:

  • Compliance (ability to expand)
  • Elastic recoil (ability to bounce back and contract)
  • Surface tension (ability to prevent collapse)
• Water surrounding alveolar allows oxygen to dissolve. However, the amount of water present impacts the diffusion distance:

  • Increase in water increases both surface tension (increasing chance of lung collapse) and diffusion distance (increases resistance)
• The pulmonary surfactant is lipoprotein produced by the type II alveolar cells. This reduces surface tension, preventing lung collapse
• Pulmonary minute ventilation = tidal volume x respiratory rate.

  
  

  Alveolar ventilation is impacted anatomical dead space (tracheal and bronchi air which doesn't exchange oxygen). Hence, alveolar ventilation = (tidal volume - dead space volume) x respiratory rate
• Increase in CO2 in area means we want to remove it by increasing air flow by dilating airways. Decrease in O2 means cells have high metabolic activity and so we want to decrease blood flow to increase oxygen uptake. This occurs through vasoconstriction
• In the atmosphere:

  • PO2 = 160 mmHg
  • PCO2 = 0.25 mmHg

  In the alveoli, PO2 decreases to 150 mmHg due to nasal dilution to warm air and then decreases to 100 mmHg due to anatomic dead space air mixing.

  In pulmonary and arterial systemic circulation:

  • PO2 = 100 mmHg
  • PCO2 = 40 mmHg

  In venous system after cell diffusion occurs:

  • PO2 = 40 mmHg
  • PCO2 = 46 mmHg
• Three factors that affect gas exchange:

  • Surface area of membrane (decrease SA in emphysema)
  • Thickness of membrane (increased thickness in fibrotic lung disease),
  • Gas diffusion constant (increased diffusion distance in pulmonary edema)
  • Gas partial pressure gradient (low P_AO2 in asthma due to bronchorestriction)
• Oxygen storage:

  • 2% dissolved in plasma
  • 98% stored in haemoglobin as oxyhaemoglobin

  Carbon dioxide storage:

  • 7% dissolved in plasma (more polar than O2)
  • 25% stored in haemoglobin as carbaminohaemoglobin
  • 70% as HCO3- due to the reaction CO2 + H2O <--> H2CO3 <--> H+ + HCO3-, catalysed by carbonic anhydrase
• Amount of dissolved O2 is directly proportional to PO2
• Haemoglobin can carry up to 4 O2 molecules and the percentage of saturated haemoglobin varies between 0-100%, depending on PO2, where higher PO2 increases saturation percentage
• Carbon monoxide decreases haemoglobin saturation percentage of oxygen since haemoglobin has a higher affinity for carbon monoxide than oxygen
• CO2 transport:

  • CO2 diffuses out of cells and dissolves in plamsa
  • Dissolved CO2 enters red blood cells, where 25% is stored in haemoglobin
  • The rest reacts with water in presence of carbonic anhydrase to form bicarbonate
  • Bicarbonate leaves red blood cell whilst chloride enters, called chloride shift
  • When CO2 diffuses out to alveoli, this shifts haemoglobin-stored CO2 to enter plasma, and also reversibly shifts bicarbonate back to CO2
• Ventilation allows CO2 to leave circulation, decreasing PCO2. Thus, hypoventilation causes hypercapnia whilst hyperventilation (in absence of bag) causes hypocapnia. This alters pH balance
• Ventilation rate and tidal volume are controlled by CNS:

  • voluntary control activates limbic system to activate medulla oblongata and pons
  • CO2 is received by medullary chemoreceptors alongside;
  • O2 and pH are received by carotid and aortic chemoreceptors, affecting oblongata and pons through afferent system
• Peripheral chemoreceptors are activated by:

  • Low PO2 (less than 60 mm Hg) closing potassium channels, increasing intracellular potassium and causing membrane depolarisation
  • Depolarisation opens voltage gated calcium channels, increasing neurotransmitter exocytosis, propagating action potential towards medullary centres
• High CO2 diffuses through blood brain barrier into cerebrospinal fluid, producing bicarbonate through carbonic anhydrase. This increase concentration of H+, received by central chemoreceptors, signalling increased ventilation to respiratory control centre
• The kidney consists of an outer cortex (tubules and bowman's capsule) and inner medulla (loop of Henle and collecting duct), with pyramid and renal column structures
• Renal blood flow: Afferent arterioles -> glomerulus -> efferent arterioles -> peritubular capillaries (vasa recta) - venules
• Three basic renal processes include:

  • Glomerular filtration
  • Tubular secretion
  • Tubular reabsorption
• 20% of the plasma is filtered from glomerulus into Bowman's capsule. This is called the filtration fraction
• Renal corpuscle = Bowman's capsule + glomerulus fused together
• There are three filtration barriers between the glomerulus and Bowman's capsule:

  • Glomerular capillary endothelium (fenestrated)
  • Basement membrane
  • Epithelium of Bowman's capsule (foot process, cytoplasmic extensions, of podocytes)
• Filtration is impacted by change in pressure, impacted by:

  • Hydrostatic pressure (due to water moving away from water)
  • Osmotic pressure (water moving towards solute)
  • Fluid pressure in capsule
• Glomerular filtration rate (mL/min) is impacted by:

  • hydrostatic pressure in glomerulus
  • Vasoconstriction of afferent arteriole and vasodilation of efferent arteriole decreases blood flow, decreasing GFR
  • Vasodilation of afferent arteriole and vasoconstriction of efferent arteriole increases blood flow, increasing GFR
  • Fluid pressure in capsule
  • Increase in capsule tubular fluid increases fluid pressure, decreasing GFR
  • Osmotic pressure
  • Increasing plasma colloid pressure or decreasing renal plasma flow rate increases osmotic pressure, decreasing GFR
• GFR is autoregulated by:

  • Myogenic response (increased blood volume increases arteriole stretch leads to vasoconstriction, increasing resistance, decreasing afferent blood flow)
  • Tubuloglomerular feedback (in another flash card)
• The tubuloglomerular feedback is governed by juxtaglomerular apparatus which is triggered by changes in distal convoluted tubule NaCl levels:

  • Higher NaCl levels: Macula dense cells detect the increase in levels, sending a paracrine signal to granular cells which secrete adenosine to vasoconstrict afferent arteriole
  • Lower NaCl levels: macula densa sends paracrine signal to granola cells to secrete NO and prostaglandin for vasodilation of afferent arteriole. Furthermore, angiotensin II is secreted causing vasoconstriction of efferent arteriole
• Plasma renal clearance (ml/min) x [plasma] = excretion rate: volume of a particular substance cleared per minute

  A similar equation can be drawn for urine: [urine] x urine flow rate = excretion rate
• Tubular reabsorption occurs through transepithelial transport, including:

  • Active transport of Na+
  • Passive transport of anions
  • Osmotic movement of water
  • Diffusive and paracellular pathway transport of K+, Ca2+, urea
• Sodium is reabsorbed primarily through active transport and secondarily through sodium-glucose linked transport.

  
  

  70% is reabsorbed in the proximal convoluted tubule, 20% in the ascending loop of Henle, 6% in the distal convoluted tubule, 3% in collecting duct and 1% remains in urine
• Whilst the cortex is isomotic (same osmolarity), osmolarity increases as you go deeper into the medulla. This causes only water to leave the descending loop on Henle into the peritubular capillaries whilst only solutes leave the ascending loop on Henle into the peritubular capillaries
• The osmotic nephron gradient is maintained by countercurrent exchange (blood flow in peritubular capillaries is opposite to that of the loop of Henle), also allowing hypoosmotic fluid to be regulated by hormones
• The three hormones regulating Na+ and water in the distal convoluted tubule and collecting duct includes:

  • Vasopressin (antidiuretic hormone - ADH)
  • Aldosterone
  • Natriuretic hormone
• Vasopressin introduces aquaporin (water channels) from the collecting duct, increasing water reabsorption and urine osmolarity. This occurs when osmolarity is greater that 280 mOsM, decreased blood pressure or decreased atrial stretch due to low blood volume