BIO 181 - Human Anatomy and Physiology II: Respiratory & Urinary System Study Guide
General Study Objectives BIO 181 - Human Anatomy and Physiology II
Chapter 22: Respiratory System
1. Functions of the Respiratory System
Gas Exchange: Primary function, involves the uptake of oxygen ( ext{O}2) from the atmosphere into the blood and the removal of carbon dioxide ( ext{CO}2) from the blood into the atmosphere.
Pulmonary Ventilation (Breathing): Movement of air into and out of the lungs.
Regulation of Blood pH: By altering the rate of CO_2 exhalation, the respiratory system can rapidly adjust blood H^+ concentrations, thereby regulating pH.
Vocalization: Air flowing past the vocal cords produces sounds.
Olfactory Sense: Contains receptors for the sense of smell in the nasal cavity.
Warmth and Humidification: Conditions inhaled air by warming it to body temperature and saturating it with water vapor.
Protection: Traps and removes pathogens and irritants from the inhaled air.
2. Overall Processes of the Respiratory System
a. Pulmonary Ventilation: The mechanical process of moving air into and out of the lungs. It consists of two phases:
Inspiration (Inhalation): Air flows into the lungs.
Expiration (Exhalation): Air flows out of the lungs.
b. External Respiration: The gas exchange that occurs between the alveoli of the lungs and the blood in the pulmonary capillaries. Oxygen diffuses from the alveoli into the blood, and carbon dioxide diffuses from the blood into the alveoli.
c. Internal Respiration: The gas exchange that occurs between the blood in the systemic capillaries and the tissue cells. Oxygen diffuses from the blood into the tissue cells, and carbon dioxide diffuses from the tissue cells into the blood.
d. Transport of Respiratory Gases: The cardiovascular system transports oxygen from the lungs to the body tissues and carbon dioxide from the tissues to the lungs.
3. Structure, Histology, and Function of Respiratory Structures
Nose/Nasal Cavities:
Structure/Function: Provides an airway, moistens and warms incoming air, filters inhaled air using vibrissae (hairs) and mucus, serves as a resonating chamber for speech, and houses olfactory receptors.
Histology: Lined primarily with respiratory mucosa (pseudostratified ciliated columnar epithelium with goblet cells) in most areas, and olfactory epithelium in the superior region.
Pharynx (Throat):
Structure/Function: Common passageway for both air and food. Connects the nasal cavity and mouth to the larynx and esophagus. Divided into three regions: nasopharynx (air only, pseudostratified ciliated columnar epithelium), oropharynx (air and food, stratified squamous epithelium), and laryngopharynx (air and food, stratified squamous epithelium).
Larynx (Voice Box):
Structure/Function: Routes air and food to appropriate channels and is the primary organ of voice production. Composed of nine cartilages (e.g., thyroid cartilage forms the Adam's apple, cricoid cartilage forms a complete ring).
Epiglottis:
Structure/Function: A spoon-shaped flap of elastic cartilage that covers the laryngeal inlet (glottis) during swallowing, preventing food and liquids from entering the trachea.
Trachea (Windpipe):
Structure/Function: Extends from the larynx into the mediastinum, dividing into two main bronchi. Provides a rigid, patent airway for air passage. Its C-shaped rings of hyaline cartilage prevent collapse, while the posterior soft tissue allows the esophagus to expand during swallowing.
Histology: Lined with pseudostratified ciliated columnar epithelium, which traps particles and moves mucus upwards.
Bronchi:
Structure/Function: The trachea branches into primary (main) bronchi, which then branch into secondary (lobar) and tertiary (segmental) bronchi. These conducting passages distribute air to the lungs. Cartilage rings become plates, and the amount of smooth muscle increases as they get smaller.
Bronchioles:
Structure/Function: Smallest conducting airways, less than 1 ext{ mm} in diameter. Lack cartilage but have a relatively thick layer of smooth muscle, allowing for significant regulation of airway diameter and airflow. Terminal bronchioles lead to respiratory bronchioles.
Lungs (Alveoli):
Structure/Function: Paired organs in the thoracic cavity. The primary sites of gas exchange are the alveoli—tiny, thin-walled air sacs surrounded by pulmonary capillaries. This structure provides a vast surface area for efficient gas exchange.
4. Respiratory System Zones
Upper Respiratory System: Includes the nose, nasal cavity, and pharynx. These structures are involved in initial air conditioning and humidification.
Lower Respiratory System: Includes the larynx, trachea, bronchi, bronchioles, and lungs (alveoli). Primarily responsible for conducting air efficiently and facilitating gas exchange.
Conducting Zone: Consists of all respiratory passages from the nose to the terminal bronchioles. Its function is to filter, warm, and humidify incoming air, ensuring it reaches the respiratory zone in an optimal state for gas exchange. No gas exchange occurs here.
Respiratory Zone: The actual site of gas exchange. It begins where terminal bronchioles feed into respiratory bronchioles, which lead to alveolar ducts and finally alveolar sacs, which contain clusters of alveoli.
5. Respiratory Membrane and Cells
Respiratory Membrane: A very thin (typically 0.2 - 0.6 ext{ extmu}m) blood-air barrier across which gas exchange occurs by simple diffusion. It's composed of three layers:
The alveolar epithelial cell (Type I pneumocyte).
The fused basal laminae of the alveolar epithelium and the capillary endothelium.
The capillary endothelial cell.
Three Cells of the Alveoli:
Type I Pneumocytes (Squamous Alveolar Cells): Form the major part of the alveolar wall, extremely thin to optimize gas diffusion. They are the primary site of gas exchange.
Type II Pneumocytes (Septal Cells): Scattered among Type I cells, these cuboidal cells secrete surfactant, a phospholipid that reduces alveolar surface tension, preventing alveolar collapse during expiration.
Alveolar Macrophages (Dust Cells): Crawl freely along the internal alveolar surfaces, phagocytizing dust particles, pathogens, and other debris that have escaped earlier defense mechanisms.
6. Pulmonary Ventilation and Gas Exchange
Pulmonary Ventilation (Breathing):
Inspiration (Inhalation):
Process: An active process. The diaphragm contracts and flattens, moving inferiorly. The external intercostal muscles contract, lifting the rib cage up and out. This increases the volume of the thoracic cavity.
Pressures: Due to Boyle's Law, the increase in thoracic volume causes intrapulmonary pressure (P{pul}) to drop below atmospheric pressure (P{atm}), creating a pressure gradient (P{pul} < P{atm}) that draws air into the lungs.
Expiration (Exhalation):
Process: A passive process during quiet breathing. The diaphragm and external intercostals relax, causing the thoracic cavity to decrease in volume. The elastic lungs recoil.
Pressures: The decrease in thoracic volume increases intrapulmonary pressure above atmospheric pressure (P{pul} > P{atm}), forcing air out of the lungs. Forced expiration involves the contraction of internal intercostals and abdominal muscles.
Gas Exchange (Internal and External Respiration):
Driving Force: Gases move down their partial pressure gradients.
External Respiration (Lungs):
Oxygen: P{O2} in alveoli ( ext{approx } 104 ext{ mmHg}) is higher than P{O2} in pulmonary capillary blood ( ext{approx } 40 ext{ mmHg}), so oxygen diffuses from alveoli into the blood.
Carbon Dioxide: P{CO2} in pulmonary capillary blood ( ext{approx } 45 ext{ mmHg}) is higher than P{CO2} in alveoli ( ext{approx } 40 ext{ mmHg}), so carbon dioxide diffuses from blood into the alveoli.
Internal Respiration (Tissues):
Oxygen: P{O2} in systemic capillary blood ( ext{approx } 95 ext{ mmHg}) is higher than P{O2} in tissue cells ($ ext{approx } 40 ext{ mmHg or less}), so oxygen diffuses from blood into the tissues.
Carbon Dioxide: P{CO2} in tissue cells ( ext{approx } 45 ext{ mmHg or more}) is higher than P{CO2} in systemic capillary blood ($ ext{approx } 40 ext{ mmHg}), so carbon dioxide diffuses from tissues into the blood.
7. Gas Laws and Their Relationship to Ventilation/Gas Exchange
Boyle’s Law: States that at constant temperature, the pressure of a gas is inversely proportional to its volume (P1V1 = P2V2).
Relationship to Ventilation: This law is fundamental to pulmonary ventilation. When lung volume increases (inspiration), intrapulmonary pressure decreases, causing air to flow in. When lung volume decreases (expiration), intrapulmonary pressure increases, causing air to flow out.
Dalton’s Law of Partial Pressures: States that the total pressure exerted by a mixture of gases is equal to the sum of the partial pressures of the individual gases in the mixture (P{total} = P1 + P2 + … + Pn).
Relationship to Gas Exchange: Explains why gases move down their individual partial pressure gradients during external and internal respiration. For example, oxygen moves from an area of higher oxygen partial pressure to an area of lower oxygen partial pressure.
Henry’s Law: States that when a gas is in contact with a liquid, the amount of gas that will dissolve in the liquid at a given temperature is proportional to its partial pressure in the gas phase and its solubility in the liquid.
Relationship to Gas Exchange: Determines how much oxygen and carbon dioxide dissolve in the blood plasma and other body fluids. For example, carbon dioxide is much more soluble in blood plasma than oxygen, allowing it to diffuse more readily even with smaller partial pressure gradients.
8. Physical Factors Affecting Pulmonary Ventilation
a. Airway Resistance: The friction or drag encountered by air as it flows through the respiratory passages. It is primarily determined by the diameter of the conducting tubes.
Influence: Bronchial smooth muscle contraction (e.g., in asthma) increases resistance, making breathing difficult. Bronchodilation decreases resistance. Resistance is typically highest in the medium-sized bronchi, not the smallest bronchioles, due to the vast branching creating a huge cross-sectional area.
b. Alveolar Surface Tension: The force exerted by the liquid film lining the alveoli, which tends to pull the alveolar walls inward and reduce their size. If unchecked, this force could cause alveoli to collapse.
Influence: Surfactant, produced by Type II pneumocytes, significantly reduces this surface tension, preventing alveolar collapse and reducing the energy needed to inflate the lungs.
c. Lung Compliance: The ease with which the lungs can be expanded. It is a measure of the distensibility of the lungs and the chest wall.
Influence: High compliance indicates that the lungs can expand easily, requiring less energy for breathing. Low compliance (e.g., due to fibrosis, pneumonia, or inadequate surfactant production) makes it harder to inflate the lungs, increasing the work of breathing.
9. Lung Volumes and Capacities
Four Major Lung Volumes:
Tidal Volume (TV): The amount of air inhaled or exhaled with each breath during normal 1, quiet breathing ( ext{approx } 500 ext{ mL}).
Inspiratory Reserve Volume (IRV): The maximal amount of air that can be forcibly inhaled beyond a tidal inspiration ( ext{approx } 2100 - 3200 ext{ mL}).
Expiratory Reserve Volume (ERV): The maximal amount of air that can be forcibly exhaled after a tidal expiration ( ext{approx } 1000 - 1200 ext{ mL}).
Residual Volume (RV): The amount of air remaining in the lungs after a maximal forced expiration. This volume ensures that the alveoli do not completely collapse and allows for continuous gas exchange ( ext{approx } 1200 ext{ mL}).
Four Major Lung Capacities (combination of two or more volumes):
Total Lung Capacity (TLC): The maximum amount of air the lungs can hold after a maximal inspiratory effort. TLC = TV + IRV + ERV + RV ( ext{approx } 6000 ext{ mL}).
Vital Capacity (VC): The maximum amount of air that can be expelled from the lungs after a maximal inspiratory effort. It represents the total amount of exchangeable air. VC = TV + IRV + ERV ( ext{approx } 4800 ext{ mL}).
Inspiratory Capacity (IC): The total amount of air that can be inhaled after a normal tidal expiration. IC = TV + IRV ( ext{approx } 2400 - 3600 ext{ mL}).
Functional Residual Capacity (FRC): The volume of air remaining in the lungs after a normal tidal expiration. FRC = ERV + RV ( ext{approx } 2400 ext{ mL}).
10. Factors Affecting External Respiration
a. Partial Pressure Gradients and Gas Solubility:
Partial Pressure Gradients: The steeper the partial pressure gradient for a gas across the respiratory membrane, the faster and greater the diffusion of that gas. Oxygen has a large gradient from alveoli to blood ( ext{O}2 ext{ in alveoli } (104 ext{ mmHg}) ext{ vs. } ext{O}2 ext{ in blood } (40 ext{ mmHg})). Carbon dioxide has a smaller gradient ( ext{CO}2 ext{ in blood } (45 ext{ mmHg}) ext{ vs. } ext{CO}2 ext{ in alveoli } (40 ext{ mmHg})).
Gas Solubility: According to Henry's Law, gases dissolve in proportion to their partial pressures and solubilities in the liquid. CO2 is about 20 times more soluble in blood plasma and alveolar fluid than O2, compensating for its smaller partial pressure gradient and allowing for nearly equal amounts of O2 and CO2 to be exchanged.
b. Thickness and Surface Area of the Respiratory Membrane:
Thickness: The thinness of the respiratory membrane (typically 0.5 - 1 ext{ extmu}m) facilitates rapid gas exchange. Any thickening (e.g., due to edema, fibrosis, or inflammatory exudates) increases the diffusion distance, significantly impairing gas exchange.
Surface Area: The vast surface area of the alveoli (approximately 70 ext{ m}^2 in healthy adults) provides ample space for gas exchange. Diseases like emphysema (destruction of alveolar walls) reduce this surface area, severely limiting gas transfer.
c. Ventilation-Perfusion Coupling:
Concept: For optimal gas exchange, there must be a close match, or coupling, between ventilation (V, the amount of gas reaching the alveoli) and perfusion (Q, the blood flow through the alveolar capillaries). The ideal V/Q ratio is 0.8.
Regulation by P{O2}: Alveolar P{O2} controls arteriolar diameter. If alveolar P{O2} is high, pulmonary arterioles dilate, increasing perfusion to that area. If alveolar P{O2} is low, arterioles constrict, diverting blood to better-ventilated alveoli.
Regulation by P{CO2}: Alveolar P{CO2} controls bronchiolar diameter. If alveolar P{CO2} is high, bronchioles dilate, increasing ventilation to expel CO2. If alveolar P{CO_2} is low, bronchioles constrict, reducing ventilation.
11. Oxygen and Carbon Dioxide Transport in the Blood
Oxygen Transport:
Bound to Hemoglobin: About 98.5%% of oxygen is transported reversibly bound to the iron atoms in the heme groups of hemoglobin (Hb) molecules within red blood cells, forming oxyhemoglobin ( ext{HbO}2). Each hemoglobin molecule can bind up to four O2 molecules.
Dissolved in Plasma: A small percentage ( ext{about } 1.5%%) of oxygen is transported dissolved directly in the plasma.
Carbon Dioxide Transport:
As Bicarbonate Ions ( ext{HCO}3^-): About 70%% of CO2 is transported in the plasma as bicarbonate ions. Inside red blood cells, CO2 combines with water to form carbonic acid ( ext{H}2 ext{CO}3), catalyzed by carbonic anhydrase. Carbonic acid quickly dissociates into H^+ and HCO3^-. The HCO_3^- then diffuses into the plasma in exchange for Cl^- (chloride shift), and the H^+ is buffered by hemoglobin.
Bound to Hemoglobin: About 20%% of CO2 is transported bound to the amino groups of hemoglobin's global chains, forming carbaminohemoglobin ( ext{HbCO}2). This binding occurs at a different site than oxygen, so CO2 and O2 do not directly compete for binding sites on hemoglobin. This is enhanced in deoxygenated blood (Haldane effect).
Dissolved in Plasma: Approximately 7-10%% of CO_2 is transported dissolved directly in the plasma.
Bicarbonate Reaction: CO2 + H2O
ightleftharpoons H2CO3
ightleftharpoons H^+ + HCO_3^-
12. pH Buffering System and Acidosis/Alkalosis
pH Buffering System: The bicarbonate buffer system is the most important chemical buffer in extracellular fluid, including blood plasma. It helps to regulate blood pH by reversibly binding H^+ ions.
Respiratory System's Role: The respiratory system can quickly adjust blood pH by altering the rate and depth of breathing, which changes the amount of CO2 (and thus carbonic acid) in the blood. Increased ventilation expels more CO2, reducing H^+ and raising pH. Decreased ventilation retains CO_2, increasing H^+ and lowering pH.
Cardiovascular System's Role: While not a direct buffer, the . cardiovascular system is essential for transporting buffer components (like bicarbonate and hemoglobin) throughout the body to sites where pH imbalances need correction and exchanging gases in lungs and tissues.
Normal Blood pH: The physiological pH range for arterial blood is 7.35 - 7.45.
Acidosis: Occurs when blood pH falls below 7.35, indicating an excess of H^+ ions.
Alkalosis: Occurs when blood pH rises above 7.45, indicating a deficiency of H^+ ions.
13. Respiratory Acidosis/Alkalosis and pH Regulation by Respiratory System
Respiratory Acidosis:
Common Situations: Arises from hypoventilation (decreased ventilation), which leads to inadequate CO2 excretion. Common causes include chronic obstructive pulmonary disease (COPD), pneumonia, asthma, opioid overdose, or injury to brainstem respiratory centers. The retained CO2 raises blood P{CO2}, shifting the bicarbonate reaction to the right and increasing H^+ concentration and lowering pH.
Regulation: The kidneys are the primary long-term compensators. They respond by increasing the reabsorption of bicarbonate ions ( ext{HCO}_3^-) and increasing the secretion of H^+ ions into the urine, thereby raising blood pH.
Respiratory Alkalosis:
Common Situations: Results from hyperventilation (excessive ventilation), which rapidly expels CO2 from the body. Causes include anxiety attacks, high altitude (hypoxia), fever, or excessive voluntary deep breathing. The decreased CO2 lowers blood P{CO2}, shifting the bicarbonate reaction to the left, decreasing H^+ concentration and raising pH.
Regulation: The kidneys compensate by decreasing HCO3^- reabsorption and increasing HCO3^- excretion in the urine, while also conserving H^+ ions, thereby lowering blood pH.
Respiratory System's Role in pH Regulation: The respiratory system provides a rapid but temporary control over blood pH by adjusting the rate of CO2 exhalation. Changes in ventilation can quickly correct imbalances by either expelling excess CO2 (in acidosis) or retaining CO2 (in alkalosis) to bring the P{CO_2} and thus H^+ concentrations back toward normal.
14. Oxygen-Hemoglobin Dissociation Curve
Significance: This curve graphically illustrates the relationship between the partial pressure of oxygen (P{O2}) and the percentage of hemoglobin saturation with oxygen. It is typically S-shaped (sigmoidal).
High P{O2} (Lungs): At high P{O2} (e.g., 100 ext{ mmHg} in the alveoli), hemoglobin is almost fully saturated with O_2, facilitating efficient loading of oxygen onto Hb.
Low P{O2} (Tissues): At lower P{O2} (e.g., 40 ext{ mmHg} in resting tissues), hemoglobin readily unloads O2, providing oxygen to metabolically active cells. The steep portion of the curve at this range allows significant O2 release with only a moderate drop in P{O2}.
Shifting of the Curve (Bohr Effect): Factors that alter hemoglobin's affinity for oxygen cause the dissociation curve to shift.
Shift to the Right (Decreased Hb Affinity for O2 / Increased O2 Unloading to Tissues):
Decreased pH (Increased H^+): Increased acidity (more H^+) weakens the Hb- ext{O}_2 bond.
Increased Temperature: Higher temperatures (>38^ ext{o} ext{C}) weaken the Hb- ext{O}_2 bond.
Increased BPG (2,3-Bisphosphoglycerate): A metabolical byproduct in RBCs, BPG binds to hemoglobin and stabilizes the deoxyhemoglobin conformation, promoting O_2 release.
Increased P{CO2}: CO2 directly binds to hemoglobin and also contributes to H^+ formation (via carbonic acid), both leading to a decreased affinity for O2.
These conditions are characteristic of metabolically active tissues, where more O_2 is needed.
Shift to the Left (Increased Hb Affinity for O2 / Decreased O2 Unloading to Tissues):
Increased pH (Decreased H^+): More alkaline conditions strengthen the Hb- ext{O}_2 bond.
Decreased Temperature: Lower temperatures (<37^ ext{o} ext{C}) strengthen the Hb- ext{O}_2 bond.
Decreased BPG: Less BPG leads to increased Hb- ext{O}_2 affinity.
Decreased P{CO2}: Less CO2 strengthens the Hb- ext{O}2 bond.
These conditions are typical of the lungs, where optimal O_2 loading is desired.
15. Control Mechanisms of Breathing
Neural Mechanisms:
Medullary Respiratory Centers: Located in the medulla oblongata, these centers generate the basic rhythm of breathing.
Ventral Respiratory Group (VRG): Contains rhythm-generating neurons that set the eupnea (normal respiratory rate of 12-15 breaths/minute). It sends inspiratory signals to the diaphragm and external intercostals, and expiratory signals during forced exhalation.
Dorsal Respiratory Group (DRG): Integrates input from peripheral chemoreceptors and stretch receptors in the lungs and sends this information to the VRG, modifying the rhythm.
Pontine Respiratory Centers (Pneumotaxic and Apneustic Centers): Located in the pons, these centers fine-tune the breathing rhythm.
Pneumotaxic Center (Pontine Respiratory Group): Transmits inhibitory impulses to the inspiratory neurons of the DRG, shortening inspiration and promoting a more rapid respiratory rate.
Apneustic Center: Provides stimulatory impulses to the inspiratory neurons, prolonging inspiration. This effect is usually overridden by the pneumotaxic center signals.
Factors that Influence Rate/Depth of Breathing:
Central Chemoreceptors: Located in the ventrolateral medulla. Highly sensitive to changes in the P{CO2} of the cerebrospinal fluid (CSF). An increase in P{CO2} (which leads to an increase in H^+ in the CSF) is the most potent stimulus for increasing breathing rate and depth.
Peripheral Chemoreceptors: Located in the aortic arch and carotid bodies. These receptors primarily respond to a substantial drop in arterial P{O2} (below 60 ext{ mmHg}) and also to increases in arterial P{CO2} and H^+ (decreased pH). They are less sensitive to O2 changes than central chemoreceptors are to CO2 changes.
Baroreceptors: Located in the carotid sinuses and aortic arch. These receptors monitor blood pressure and can have an indirect influence on breathing by affecting cardiovascular function, which can then alter blood flow to respiratory centers.
Irritant Receptors: Located in the airway mucosa. Respond to inhaled irritants (e.g., dust, pollen, noxious fumes), triggering reflex constriction of bronchioles and/or coughing/sneezing to expel the irritants.
Stretch Receptors (Hering-Breuer Reflex): Located in the visceral pleura and airway smooth muscle. Activated when the lungs become excessively stretched during inspiration. They send inhibitory signals to the inspiratory centers via the vagus nerves, preventing overinflation of the lungs.
16. Effects of Exercise and Altitude on Respiration
Exercise:
Hyperpnea: During exercise, ventilation rate and depth increase significantly (hyperpnea), often ext{10-20} times the resting rate, to match the increased metabolic production of CO2 and consumption of O2 by working muscles.
Mechanisms: The increase in ventilation is precisely regulated. Primary stimuli include:
Neural Input: Psychological stimuli (anticipation), cortical motor neuron activation during muscle contraction, and proprioceptor activation in muscles and joints from movement.
Chemical Stimuli: While arterial P{O2} and P{CO2} remain surprisingly stable during moderate exercise, muscle activity can produce localized increases in P{CO2}, H^+ (from lactic acid), and temperature, which all stimulate chemoreceptors.
Efficiency: The respiratory system is highly efficient during exercise, allowing arterial blood gas levels to remain relatively constant, which is remarkable given the huge increase in gas exchange.
Altitude (High Altitude Adaptation/Acclimatization):
Hypoxia: At high altitudes, the atmospheric pressure is lower, leading to a decrease in the partial pressure of inspired O2 (P{I O2}). This results in lower alveolar P{O2} and, consequently, lower arterial P{O_2} (hypoxemia).
Initial Response (Acute):
Hyperventilation: The peripheral chemoreceptors (primarily carotid bodies) are very sensitive to the drop in arterial P{O2} and stimulate an immediate increase in breathing rate and depth. This helps to increase alveolar P{O2}.
Respiratory Alkalosis: The increased ventilation expels more CO2, causing a decrease in arterial P{CO_2} and leading to respiratory alkalosis (increased blood pH).
Acclimatization (Chronic, Days to Weeks):
Renal Compensation: The kidneys respond to respiratory alkalosis by excreting more bicarbonate ions ( ext{HCO}_3^-) and retaining H^+, which slowly normalizes blood pH.
Erythropoiesis: The prolonged hypoxia stimulates the kidneys to release erythropoietin (EPO), which increases red blood cell production in the bone marrow. This leads to polycythemia (increased RBC count), enhancing the O_2 carrying capacity of the blood.
Increased BPG: The production of 2,3-bisphosphoglycerate (BPG) by red blood cells increases, shifting the oxygen-hemoglobin dissociation curve to the right. This reduces hemoglobin's affinity for O2, facilitating O2 unloading to tissues at lower P{O2}.
Angiogenesis: Increased vascularization of tissues may also occur over long periods.
Chapter 25: Urinary System
17. Functions of the Urinary System
Regulation of Water Balance: Kidneys regulate the total volume of water in the body, primarily influencing blood volume and blood pressure.
Regulation of Ion Balance: Controls the levels of various ions in the blood, such as \text{Na}^+, \text{K}^+, \text{Ca}^{2+}, \text{Cl}^-, and phosphate ions.
Regulation of Acid-Base Balance (pH): Kidneys regulate blood pH by excreting H^+ ions and conserving bicarbonate ions (\text{HCO}_3^-), or vice versa, especially important for long-term pH management.
Excretion of Metabolic Wastes: Removes nitrogenous wastes such as urea (from protein metabolism), creatinine (from muscle creatine phosphate breakdown), and uric acid (from nucleic acid metabolism).
Regulation of Red Blood Cell Production: Produces erythropoietin, a hormone that can stimulates red blood cell formation in the bone marrow.
Regulation of Blood Pressure: Releases renin, an enzyme that initiates the renin-angiotensin-aldosterone mechanism, a key regulator of blood pressure.
Activation of Vitamin D: Converts vitamin D to its active form, calcitriol, which is essential for calcium absorption in the gut.
Gluconeogenesis: Under conditions of prolonged fasting, the kidneys can synthesize glucose from non-carbohydrate precursors.
18. Components of the Urinary System
Kidneys: Two bean-shaped organs that filter blood and produce urine.
Ureters: Two tubes that transport urine from the kidneys to the urinary bladder.
Urinary Bladder: A muscular sac that temporarily stores urine.
Urethra: A tube that carries urine from the urinary bladder to the outside of the body.
19. Renal Blood Supply from the Aorta to the Inferior Vena Cava
Aorta
Renal Artery
Segmental Arteries
Interlobar Arteries (between renal pyramids)
Arcuate Arteries (arch over the bases of the pyramids)
Cortical Radiate Arteries (Interlobular Arteries) (radiate into the renal cortex)
Afferent Arterioles
Glomerulus (capillary bed within the renal corpuscle where filtration occurs)
Efferent Arterioles
Peritubular Capillaries (surround cortical nephrons) OR Vasa Recta (surround juxtamedullary nephrons)
Cortical Radiate Veins (Interlobular Veins)
Arcuate Veins
Interlobar Veins
Renal Vein
Inferior Vena Cava
20. Kidney Anatomy and Function
Cortex: The outermost layer of the kidney. It is typically light-colored and granular, containing the renal corpuscles, proximal and distal convoluted tubules of the nephrons. Site of most blood filtration.
Medulla: The inner region of the kidney, darker and reddish-brown. It contains the cone-shaped renal pyramids and the loops of Henle and collecting ducts of the nephrons. Involved in concentrating urine.
Pelvis: A funnel-shaped tube, continuous with the ureter, located within the renal sinus. It collects urine from the major calyces and channels it into the ureter.
Hilum: The medial indentation of the kidney, where the renal artery and nerves enter, and the renal vein and ureter exit. It's the point of entry/exit for structures serving the kidney.
Calyx (Minor and Major): Cup-shaped structures that collect urine. Minor calyces (approx. 4-13) collect urine from the papillae of the renal pyramids. Two or three minor calyces merge to form a major calyx. Major calyces converge to form the renal pelvis.
Renal Pyramid: Cone-shaped tissue masses located in the renal medulla. They contain parallel bundles of collecting ducts and loops of Henle, giving the medulla its striated appearance.
Renal Papilla: The apex (tip) of a renal pyramid, which points towards the renal pelvis. Urine drains from the collecting ducts here into the minor calyces.
Renal Columns: Inward extensions of the renal cortex that separate the renal pyramids within the medulla. They provide support for blood vessels.
21. Nephron Types and Structures
Nephron: The structural and functional unit of the kidney, responsible for forming urine. Each kidney contains over 1 million nephrons.
Cortical Nephrons: Represent about 85\% of all nephrons. They have short loops of Henle that lie largely within the cortex or barely penetrate into the outer medulla. Their efferent arterioles give rise to extensive peritubular capillaries that surround the PCT and DCT.
Juxtamedullary Nephrons: Account for about 15\% of nephrons. They have long loops of Henle that extend deep into the renal medulla, crucial for establishing the medullary osmotic gradient used to produce concentrated urine. Their efferent arterioles give rise to vasa recta.
Components of the Nephron and Surrounding Structures:
Glomerulus: A tuft of fenestrated capillaries housed within the glomerular capsule. It is the site of blood filtration, allowing large amounts of fluid and small solutes to pass from the blood into the glomerular capsule.
Bowman’s Capsule (Glomerular Capsule): A cup-shaped hollow structure that completely surrounds the glomerulus. It has a parietal layer (simple squamous epithelium) and a visceral layer, which clings to the glomerular capillaries.
Podocytes: Highly specialized, octopus-like cells with elaborate branching processes (foot processes, or pedicels) that make up the visceral layer of Bowman's capsule. The pedicels interdigitate, leaving filtration slits between them, through which filtrate passes into the capsular space.
Renal Corpuscle: Consists of the glomerulus and Bowman's capsule. It is the initial filtering component of the nephron.
Proximal Convoluted Tubule (PCT): The first, highly coiled segment of the renal tubule, located in the cortex. Lined with cuboidal cells that have dense microvilli (brush border) and numerous mitochondria, indicating its role in extensive reabsorption (e.g., 65\% of NaCl and water, all glucose) and some secretion.
Loop of Henle (Nephron Loop): Extends from the PCT into the medulla and then back into the cortex to join the DCT. It has a descending limb (permeable to water) and an ascending limb (impermeable to water, but actively transports solutes). Crucial for creating a concentration gradient in the medulla.
Distal Convoluted Tubule (DCT): A coiled segment in the cortex following the loop of Henle. Cells have fewer microvilli and mitochondria than PCT cells. It is involved in more selective, hormonally regulated reabsorption (e.g., Na^+ by aldosterone, \text{Ca}^{2+} by PTH) and secretion.
Collecting Duct: Receives filtrate from multiple DCTs and runs through the renal medulla to the renal papilla. It is responsible for fine-tuning water reabsorption (under ADH control) and regulating Na^+ and K^+ balance (under aldosterone control), and some urea reabsorption.
Peritubular Capillaries: Low-pressure capillaries arising from efferent arterioles of cortical nephrons. They cling closely to the renal tubules in the cortex and are involved in reclaiming reabsorbed substances and carrying away secreted substances.
Vasa Recta: Long, straight vessels that arise from efferent arterioles of juxtamedullary nephrons. They run parallel to the long loops of Henle deep into the medulla. They help maintain the osmotic gradient of the renal medulla but do not reabsorb as much.
Juxtaglomerular Apparatus (JGA): A specialized structure located where the distal tubule lies against the afferent arteriole. It plays a critical role in regulating the rate of filtrate formation and systemic blood pressure.
22. Histological Differences in Nephron Segments
Glomerular Capsule (Parietal Layer): Composed of simple squamous epithelium, which is a structural outer layer. The visceral layer contains foot processes (pedicels) of podocytes around the capillaries, forming the filtration membrane. Function: Filtration of blood.
Proximal Convoluted Tubule (PCT): Lined by simple cuboidal epithelial cells with prominent, dense microvilli (brush border) on the apical surface, significantly increasing surface area for reabsorption. Abundant mitochondria are present to support active transport. Function: Bulk reabsorption of water, ions, all nutrients, and secretion of some wastes.
Nephron Loop (Loop of Henle):
Thin Descending and Thin Ascending Limbs: Composed of simple squamous epithelium. The thin descending limb is highly permeable to water. The thin ascending limb is permeable to solutes but not water. Function: Establishes the medullary osmotic gradient.
Thick Ascending Limb: Lined by cuboidal or low columnar cells, often without a significant brush border, but with numerous mitochondria needed for active transport of ions. Function: Active reabsorption of \text{Na}^+, \text{K}^+, ext{ and } \text{Cl}^-.
Distal Convoluted Tubule (DCT): Lined by simple cuboidal epithelial cells, but smaller than PCT cells and with sparse, shorter microvilli. Fewer mitochondria than PCT. Function: Regulated reabsorption and secretion based on hormonal signals (e.g., aldosterone, ADH, PTH).
Collecting Duct: Composed of two cell types:
Principal Cells: Cuboidal to columnar cells with sparse, short microvilli. Involved in maintaining water and Na+/K+ balance. Targets for ADH and aldosterone.
Intercalated Cells: Cuboidal cells with abundant microvilli. Play a role in acid-base balance by regulating H^+ and \text{HCO}_3^- secretion/reabsorption. Function: Final fine-tuning of urine concentration and composition.
23. Juxtaglomerular Complex (JGC) and Cells
Function of JGC: Regulates the rate of filtrate formation and systemic blood pressure.
Three Types of Cells Found in JGC:
Macula Densa Cells: Tall, closely packed chemoreceptor cells in the wall of the ascending limb of the loop of Henle (part of the DCT). They sense the NaCl concentration of the filtrate entering the DCT. If NaCl concentration is low (indicating low GFR), they signal the granular cells to release renin and cause vasodilation of the afferent arteriole. ‘
Granular Cells (Juxtaglomerular Cells): Enlarged smooth muscle cells in the wall of the afferent (and sometimes efferent) arteriole. They act as mechanoreceptors that sense blood pressure in the afferent arteriole. When blood pressure is low, they secrete renin, an enzyme essential for the renin-angiotensin-aldosterone system.
Extraglomerular Mesangial Cells (Lacis Cells): Cells located in the space between the afferent and efferent arterioles and the macula densa. They are believed to pass regulatory signals between the macula densa and the granular cells. They may also have phagocytic and contractile properties.
24. Blood Plasma, Glomerular Filtrate, and Urine Characteristics
Characteristic | Blood Plasma | Glomerular Filtrate | Urine |
|---|---|---|---|
Composition | Water, proteins (albumin, globulins), electrolytes, glucose, amino acids, hormones, gases, wastes | Water, electrolytes, glucose, amino acids, vitamins, hormones, nitrogenous wastes (virtually protein-free and cell-free) | Water (>$ 95\%$), urea, creatinine, uric acid, excess i,: , @ ons (\text{Na}^+, \text{K}^+, \text{PO}4^{3-}, \text{SO}4^{2-}), negligible protein/glucose |
Volumes | ~$2.7 - 3.0 ext{ L}$ (total blood plasma) | ~$120-125 ext{ mL/min}$ or ~$180 ext{ L/day}$ | ~$0.8 - 1.8 ext{ L/day}$ (average ~$1.5 ext{ L/day}$), highly variable |
Specific Gravity | ~$1.025 ext{ (due to proteins)}$ | ~$1.010 ext{ (same as protein-free plasma)}$ | ~$1.003 - 1.030$ (varies with hydration) |
pH | ~$7.35 - 7.45$ | ~$7.4$ | ~$4.5 - 8.0$ (average ~$6.0$) |
Ionic Concentrations | High \text{Na}^+, \text{Cl}^-, \text{HCO}_3^- | Similar to plasma, but without large proteins | Highly variable based on diet and hydration |
Waste Products | Urea, creatinine, uric acid (being transported) | Urea, creatinine, uric acid (present, about to be processed) | Urea, creatinine, uric acid (excreted) |
Anion Gap of the Blood: Represents the difference between the sum of measured cations (primarily \text{Na}^+ and \text{K}^+) and the sum of measured anions (primarily \text{Cl}^- and \text{HCO}_3^-) in the serum. Normal range is typically \text{10-14 mEq/L}. It reflects the concentration of unmeasured anions (e.g., proteins, phosphate, sulfate, lactate, ketoacids).
Regulation by Kidneys: The kidneys play a critical role in maintaining the anion gap by excreting excess acids or bases and regulating bicarbonate levels. An elevated anion gap usually indicates metabolic acidosis due to an accumulation of unmeasured acids.
25. Structures and Events Involved in Urine Formation
1. Filtration (Glomerular Filtration):
Description: A non-selective, passive process where water and solutes smaller than plasma proteins are forced from the blood in the glomerulus into the Bowman's capsule, forming a protein-free filtrate. Driven by hydrostatic pressure.
Filtration Membrane: A porous membrane composed of three layers:
Fenestrated Glomerular Endothelium: Allows all blood components except cells to pass through.
Basement Membrane: A fused basal lamina of the endothelium and podocytes, which prevents passage of large proteins.
Foot Processes of Podocytes (with Filtration Slits): The spaces between podocyte foot processes that allow filtrate to pass into the capsular space.
Net Filtration Pressure (NFP): The total pressure that promotes filtrate formation. It is the sum of forces favoring filtration (\text{glomerular hydrostatic pressure, } HPg) and forces opposing filtration (\text{colloid osmotic pressure in glomerulus, } OPg and \text{capsular hydrostatic pressure, } HP_c).
NFP = HPg - (OPg + HP_c) ( ext{approx } 10 ext{ mmHg}).
Glomerular Filtration Rate (GFR): The volume of filtrate formed per minute by all the glomeruli in both kidneys combined ( ext{approx } 120-125 ext{ mL/min} ext{ or } 180 ext{ L/day}). GFR is directly proportional to NFP.
2. Reabsorption (Tubular Reabsorption):
Description: A selective process where many useful substances (water, glucose, amino acids, ions) are moved from the filtrate in the renal tubules and collecting ducts back into the blood of the peritubular capillaries or vasa recta. Can be active or passive (e.g., osmosis for water).
Obligatory Reabsorption: Occurs in the proximal convoluted tubule (PCT) and the descending limb of the loop of Henle. Water reabsorption follows solute reabsorption (primarily \text{Na}^+) passively via osmosis, regardless of the body's hydration needs. It is not hormonally regulated.
Facultative Reabsorption: Occurs mainly in the distal convoluted tubule (DCT) and collecting duct. The amount of water and specific ions reabsorbed here is regulated by hormones (e.g., ADH regulates water, aldosterone regulates \text{Na}^+ and \text{K}^+), allowing the body to fine-tune urine concentration and electrolyte balance based on physiological demand.
3. Secretion (Tubular Secretion):
Description: A selective process where substances are moved from the blood (peritubular capillaries) or tubular cells directly into the filtrate in the renal tubule. This process is crucial for:
Disposing of substances (e.g., certain drugs, metabolic wastes) that were not adequately filtered.
Eliminating undesirable substances that have been reabsorbed passively (e.g., urea).
Ridding the body of excess \text{K}^+.
Controlling blood pH by secreting excess H^+ or bicarbonate ions.
26. Regulatory Functions (Intrinsic and Extrinsic Mechanisms)
Intrinsic Mechanisms (Renal Autoregulation): Act locally within the kidney to maintain a relatively constant GFR despite fluctuations in systemic blood pressure (80 - 180 ext{ mmHg}).
Myogenic Mechanism: A property of smooth muscle. When renal blood pressure increases, the afferent arteriole stretches, causing the smooth muscle in its wall to contract. This vasoconstriction limits blood flow to the glomerulus, preventing large increases in GFR. Conversely, decreased blood pressure leads to vasodilation, increasing blood flow and maintaining GFR.
Tubuloglomerular Feedback Mechanism: Involves the juxtaglomerular apparatus. The macula densa cells of the DCT sense the NaCl concentration in the filtrate. If GFR is high, filtrate flow rate is fast, and there's too little time for NaCl reabsorption, resulting in high NaCl concentration at the macula densa. This triggers the release of vasoconstrictor chemicals (e.g., ATP, adenosine) from macula densa cells, which constrict the afferent arteriole, reducing GFR. When GFR is low, the opposite occurs.
Extrinsic Mechanisms (Neural and Hormonal Controls): Override intrinsic controls when systemic blood pressure falls below 80 ext{ mmHg} or rises above 180 ext{ mmHg}. They primarily regulate systemic blood pressure, which, in turn, affects GFR.
Neural Mechanisms (Sympathetic Nervous System):
Under conditions of severe stress (e.g., hemorrhage, vigorous exercise), the sympathetic nervous system releases norepinephrine and adrenal medulla releases epinephrine.
These neurohormones cause strong vasoconstriction of afferent arterioles, greatly reducing renal blood flow and GFR. This diverts blood to other essential organs and reduces urine output, helping to increase systemic blood pressure.
Hormonal Mechanisms:
Renin-Angiotensin-Aldosterone System (RAAS): The body's main mechanism for increasing blood pressure and blood volume during low blood pressure conditions.
Renin Release: Granular cells of the JGA release renin in response to low blood pressure (less stretch of afferent arteriole), low NaCl in filtrate (detected by macula densa), or sympathetic nervous system stimulation.
Angiotensin II Formation: Renin converts angiotensinogen (a plasma protein) into angiotensin I. Angiotensin-converting enzyme (ACE) in lung capillaries converts angiotensin I to angiotensin II.
Effects of Angiotensin II: A potent vasoconstrictor (increases systemic BP), stimulates aldosterone release (increases \text{Na}^+ reabsorption), stimulates ADH release (increases water reabsorption), and directly increases proximal tubular Na+ reabsorption. All these actions increase blood volume and pressure, thereby restoring GFR.
Aldosterone: A mineralocorticoid hormone released by the adrenal cortex. Its secretion is stimulated by angiotensin II and high plasma \text{K}^+ levels. It targets the principal cells of the collecting ducts and DCT, increasing the reabsorption of \text{Na}^+ (and consequently water) and the secretion of \text{K}^+. This increases blood volume and pressure.
Antidiuretic Hormone (ADH) / Vasopressin: Released from the posterior pituitary in response to increased plasma osmolarity (dehydration) or decreased blood volume/pressure. ADH acts on the collecting ducts, increasing their permeability to water by inserting aquaporin channels, leading to increased water reabsorption and the production of a concentrated urine. This helps conserve water and increase blood volume.
Atrial Natriuretic Peptide (ANP): A hormone released by cardiac atrial cells in response to high blood volume or pressure. ANP has opposite effects to those of ADH and aldosterone:
It inhibits \text{Na}^+ reabsorption by the collecting ducts.
It suppresses the release of renin, ADH, and aldosterone.
It promotes vasodilation of afferent arterioles and constricts efferent arterioles, thereby increasing GFR.
Overall effect: Decreases blood \text{Na}^+ concentration, blood volume, and blood pressure, leading to greater urine output.
27. Respiratory vs. Metabolic Acidosis/Alkalosis
Respiratory Acidosis / Alkalosis: As described in point 13, these conditions involve pH imbalances due to abnormal P{CO2} levels caused by respiratory dysfunction.
Regulation by Renal System (Compensation):
Respiratory Acidosis: Kidneys compensate by increasing the reabsorption of bicarbonate ions (\text{HCO}_3^-) and increasing the excretion of H^+ in the urine to raise blood pH toward normal. This is a slow but powerful compensatory mechanism, taking days.
Respiratory Alkalosis: Kidneys compensate by decreasing \text{HCO}_3^- reabsorption and increasing its excretion, along with conserving H^+ ions, to lower blood pH toward normal. This also takes days.
Metabolic Acidosis / Alkalosis: These conditions involve pH imbalances due to reasons other than P{CO2} changes, primarily abnormalities in bicarbonate (\text{HCO}_3^-) levels or the accumulation of non-carbonic acids.
Metabolic Acidosis:
Cause: Characterized by low blood pH (<7.35) and low \text{HCO}_3^- levels. Common causes include:
Accumulation of metabolic acids (e.g., lactic acidosis from anaerobic respiration, ketoacidosis from uncontrolled diabetes).
Excessive loss of \text{HCO}_3^- (e.g., severe diarrhea).
Renal failure (inability to excrete H^+ and reabsorb \text{HCO}_3^-).
Regulation (Compensation):
Respiratory System: Compensates rapidly by increasing respiratory rate and depth (hyperventilation) to blow off CO2. This reduces P{CO_2}, shifting the bicarbonate reaction to the left, which lowers H^+ and raises pH towards normal.
Renal System: The kidneys attempt to compensate by increasing the secretion of H^+ and increasing the reabsorption of \text{HCO}3^- (and generating new \text{HCO}3^-).
Metabolic Alkalosis:
Cause: Characterized by high blood pH (>7.45) and high \text{HCO}_3^- levels. Common causes include:
Loss of H^+ (e.g., prolonged vomiting of stomach acid, excessive diarrhea).
Excessive intake of alkaline substances (e.g., antacids).
Regulation (Compensation):
Respiratory System: Compensates by decreasing respiratory rate and depth (hypoventilation) to retain CO2. This increases P{CO_2}, shifting the bicarbonate reaction to the right, which increases H^+ and lowers pH towards normal.
Renal System: The kidneys attempt to compensate by decreasing H^+ secretion and increasing \text{HCO}_3^- excretion in the urine.
28. Excretory Organs and Micturition
Kidneys: Filter blood to produce urine. (Structure and function detailed in sections 20-23).
Ureters:
Function: Slender tubes that convey urine from the kidneys to the urinary bladder.
Structure/Histology: Composed of three layers:
Mucosa: Lined with transitional epithelium, which is highly distensible.
Muscularis: Two layers of smooth muscle (inner longitudinal, outer circular) that generate peristaltic waves to propel urine. A third, outer longitudinal layer appears in the distal third of the ureter.
Adventitia: An outer fibrous connective tissue covering. The ureters enter the bladder obliquely, which mechanically compresses the distal ends of the ureters, preventing backflow of urine during bladder contraction.
Urinary Bladder:
Function: A collapsible muscular sac that temporarily stores urine.
Structure/Histology: The wall has three layers:
Mucosa: Lined with transitional epithelium, allowing for significant distension.
Detrusor Muscle: Three layers of smooth muscle collectively called the detrusor muscle. It contracts to expel urine from the bladder.
Adventitia (or Serosa superiorly): Outer fibrous layer.
Trigone: A smooth, triangular region on the bladder floor outlined by the openings for the ureters and the urethra. It is clinically important because infections tend to persist in this region.
Urethra:
Function: A muscular tube that drains urine from the bladder and conveys it out of the body.
Structure/Histology:
Lining: Primarily pseudostratified columnar epithelium, which changes to stratified squamous epithelium near the external opening.
Sphincters:
Internal Urethral Sphincter: Involuntary smooth muscle sphincter, keeps the urethra closed when urine is not being passed.
External Urethral Sphincter: Voluntary skeletal muscle sphincter, surrounds the urethra as it passes through the pelvic floor. Provides conscious control over urination.
Differences in Males and Females:
Female Urethra: Short (approx. 3-4 ext{ cm}). Strictly a urinary passageway.
Male Urethra: Long (approx. 15-20 ext{ cm}). Has three regions (prostatic, membranous, spongy) and carries both urine and semen (part of the reproductive system).
Micturition (Urination/Voiding):
Process: The act of emptying the bladder. It is initiated by a reflex but can be consciously controlled by adults.
Three Events that Must Occur:
Detrusor Muscle Contraction: The detrusor muscle must contract forcibly, usually under parasympathetic nervous system control.
Internal Urethral Sphincter Opening: The involuntary internal urethral sphincter must open.
External Urethral Sphincter Opening: The voluntary external urethral sphincter must open.
Control: As urine accumulates, stretch receptors in the bladder wall are activated. Signals travel to the sacral spinal cord, initiating a reflex arc that parasympathetically stimulates the detrusor muscle to contract and the internal sphincter to relax. Higher brain centers (pontine storage and micturition centers) can either inhibit the reflex or permit micturition by relaxing the external sphincter, allowing voluntary control after infancy.
29. Major Disorders Associated with the Urinary System
Renal Calculi (Kidney Stones):
Description: Hard, crystalline mineral deposits that can form in the renal pelvis. They typically consist of calcium oxalate, uric acid, or struvite. If they become large enough to obstruct the ureter, they can cause excruciating pain (renal colic) as they pass.
Causes: Dehydration, abnormal pH of urine, frequent urinary tract infections, metabolic disturbances (e.g., hypercalcemia, hyperuricemia), and genetic predisposition.
Benign Prostatic Hyperplasia (BPH):
Description: A non-cancerous enlargement of the prostate gland, common in older men. As the prostate enlarges, it can compress the urethra, obstructing urine flow from the bladder.
Symptoms: Urinary frequency, urgency, nocturia (waking at night to urinate), weak or interrupted urine stream, difficulty starting urination, and a feeling of incomplete bladder emptying. Severe cases can lead to urinary retention and kidney damage.
Urinary Tract Infections (UTIs):
Description: Bacterial infections of any part of the urinary system. They are more common in females due to their shorter urethra, which provides a shorter path for bacteria (most commonly E. coli) to ascend from the perineum into the bladder.
Symptoms: Dysuria (painful urination), urgency, frequency, cloudy and/or foul-smelling urine, hematuria (blood in urine), and sometimes fever or flank pain (if the infection has ascended to the kidneys, known as pyelonephritis).
Progression: Infections typically start in the urethra (urethritis), ascend to the bladder (cystitis), and can further ascend to the ureters and kidneys (pyelonephritis), which is a more serious condition.