Final

Question 1

Explain physical barriers using specific examples.

Answer 1

• Anatomical and physiological mechanisms that prevent entry of foreign organisms and substances.
  
  • Structural → prevent pathogens from entering body (e.g., skin with stratified epithelial layer and secretions and hair that keeps hazards away from skin)
  • Chemical secretions → neutralize and destroy pathogens (e.g., lysozyme, stomach acid)
    
    • Mucous membranes line the digestive, respiratory, urinary and reproductive tracts to provide protection.

Question 2

Explain the different roles and common origins of WBCs and classify different types according to lineage and/or function.

Answer 2

• WBCs are borne from hematopoietic red bone marrow.

Question 3

Define innate immunity and illustrate with examples.

Answer 3

• Innate responses are non-specific → react to any threat detected → present from birth

Question 4

Define adaptive immunity and illustrate with specific examples.

Answer 4

• Adaptive responses are specific and powerful → triggered by exposure to antigens → must be ‘learned’

Question 5

Identify at least three examples of immune cells living in non-immune tissue.

Answer 5

• Immune cells identified in the heart either reside or infiltrate heart tissue and include macrophages, mast cells, monocytes, neutrophils, eosinophils, B cells, and T cells
• Lungs are potent immune organs and contain macrophages, which may be divided into alveolar macrophages (AM) and interstitial macrophages (IMs), alveolar and bronchial epithelial cells (AECs and BECs), DCs, NK cells along with other ILCs (ILC1s, ILC2s, and ILC3s), and adaptive immune cells (different T and B cells).
• In human kidneys, 47% ± 12% (maximum 63%) of immune cells were CD3⁺ T cells. Kidney CD4⁺ and CD8⁺ T cells comprised 44% and 56% of total T cells.

Question 6

Describe the components of the lymphatic system.

Answer 6

• Lymph → fluid connective tissue
• Lymphatic vessels → structures that absorb fluid that diffuses from blood vessel capillaries into surrounding tissues
• Lymph nodes → filter lymph of pathogens and waste; house lymphocytes; act as staging posts for generating adaptive immune responses to antigens detected by the innate immune system.
• Thymus → main origin of T-cells, responsible for cell-mediated immunity
• Spleen → filters blood of damaged cells, waste and pathogens; site of B cell maturation
• Bone marrow → blood cell production
• Tonsils → protect digestive tract and lungs from pathogens entering the mouth or nose.

Question 7

Explain the overlap and distinctions between the lymphatic system and the immune system.

Answer 7

• The immune system, which protects the body from pathogens, is a physiological grouping → closely intertwined with the lymphatic system.

Question 8

Explain the distinction between primary and secondary in the lymphatic system.

Answer 8

• Secondary lymph tissue (e.g., spleen, lymph nodules/MALTs) contain aggregations of lymphocytes that act like lymph nodes but are not directly connected to the lymphatic system.
  
  • No capsule, no a/efferent vessels
  • The spleen filters blood plasma not lymph, acting like a lymph node for the blood.

Question 9

Explain the distinction between organ and tissue in the lymphatic system.

Answer 9

The category can be further subdivided into primary lymphoid organs, which support lymphocyte production and development, and secondary lymphoid organs, which support lymphocyte storage and function. Lymphoid tissues are concentrations of lymphocytes and other immune cells within other organs of the body.

Question 10

Explain cell-mediated immune responses using specific examples.

Answer 10

• Innate and adaptive responses that rely on WBC activity.
  
  • Innate → cell recruitment to injured tissue with release of proinflammatory mediators
  • Adaptive → activation and clonal expansion of lymphocytes

Question 11

Classify as physical barrier or chemical secretion:

Multiple layers of cells in an unkeratinized stratified squamous epithelium.

Answer 11

Physical barrier.

Question 12

Classify as physical barrier or chemical secretion:

Cilia in the respiratory tract

Answer 12

Physical barrier

Question 13

Classify as physical barrier or chemical secretion:

The BBB

Answer 13

Physical barrier.

Question 14

Classify as physical barrier or chemical secretion:

Secretion of anti-bacterial chemicals by sweat gland cells

Answer 14

Physical barrier.

Question 15

Classify as physical barrier or chemical secretion:

Secretion of anti-bacterial peptides by a neutrophil

Answer 15

Chemical secretion

Question 16

Classify as physical barrier or chemical secretion:

Acidic secretions in the vagina

Answer 16

Physical barrier

Question 17

Which WBC is both myeloid and phagocytic?

Answer 17

Neutrophils

Monocytes

Question 18

Which WBC is both myeloid and non-phagocytic?

Answer 18

Mast cell

Question 19

Which WBC is both myeloid and involved in innate immunity?

Answer 19

Monocyte

Question 20

Which WBC is both lymphoid and involved in innate immunity?

Answer 20

Natural killer cell

Question 21

Which WBC is both lymphoid and involved in adaptive immunity?

Answer 21

T and B cells

Question 22

Which WBC is both myeloid and involved in adaptive immunity?

Answer 22

Dendritic cell

Question 23

Lymph vessels, like blood vessels, have a simple squamous epithelial wall.

True or False?

Answer 23

True.

Question 24

There is no way to pump lymph through lymph vessels.

True or False?

Answer 24

False. They have a smooth muscle layer that can create pumping action.

Question 25

All lymphocytes are WBCs and are borne in bone marrow. True or false?

Answer 25

True.

Question 26

Mature lymphocytes are only found in the vessels and organs of the lymphatic system. True or False?

Answer 26

False.

Question 27

Why would local lymph nodes be the first target to check for metastatic cancers? Explain the purpose of the dye injection before the biopsy – why take this extra step (e.g., why not just target lymph nodes randomly, or all lymph nodes?)

Answer 27

Cancer cells migrating would be present in lymph fluid and be filtered out into nodes. Specific tissues drain into specific nodes. Taking out lymph nodes, or damaging lymph vessels can lead to serious problems, so avoidance of damaging them is paramount. Thus, figuring out exactly which lymph nodes should be biopsied is the best practice.

Question 28

Describe components of the innate immune system and give examples of each.

Answer 28

* Physical barriers * Phagocytes * Immune surveillance * Interferons * Complement * Inflammation * Fever

Question 29

Describe phagocytes.

Answer 29

* **Phagocytes** remove cellular debris and respond to foreign substances that have breached the physical defences * Myeloid lineage; includes: * Neutrophils * Eosinophils * Macrophages

Question 30

What are the 3 steps to elicit an inflammatory response?

Answer 30

* **Recognition** → body senses/detects pathogens/abnormal cells * **Structural changes** → local tissue and vasculature become more permissive to infiltration by responding immune cells; vessels become ‘leaky’ * **Recruitment** → further innate immune cells are recruited and over the next few weeks the adaptive immune system is activated

Question 31

Describe the function of complement.

Answer 31

* Complement forms the membrane attack complex which pokes holes in bacterial cell membranes leading to its lysis. * 3 pathways to activation, all leading to * Cell lysis → via MAC * Opsonization → enhanced phagocytosis * Inflammation → histamine release

Question 32

Define what a cytokine is, list the 3 major classes.

Answer 32

* Cytokines are a family of small peptides which coordinate immune responses; may also act as hormones. * Classes include interferons, interleukins, and tumour necrosis factors.

Question 33

Outline the major steps involved in the innate response to an acute bacterial infection and predict the effects of interfering with its components.

Answer 33

* **Immediate phase** → response to pathogen by proteins and immune cells already present in blood/tissues; e.g., neutrophils, eosinophils, fixed macrophages * **Induced phase** → recruitment of phagocytes from bloodstream; uses soluble signals to attract more immune cells * Together = inflammatory response

Question 34

What are the cardinal signs of inflammation? [5]

Answer 34

* Pain * Heat * Swelling * Redness * Loss of function

Question 35

Describe NK cells.

Answer 35

* NK cells release toxic granules to destroy target cells (i.e., do not phagocytose them) → myeloid lineage. * Perforin released from NK cells pokes holes in target cell which leads to its lysis.

Question 36

Compare neutrophils and eosinophils.

Answer 36

* **Neutrophils** → the first responders to infection * Very abundant * 3-7 lobes * Target bacterial cells and debris * **Eosinophils** * Relatively few * 2 lobes * Target molecules covered with antibodies * Both → myeloid lineage

Question 37

Compare fixed and free macrophages.

Answer 37

**Fixed** → permanent residents of tissues/organs; live in connective tissue **Free** → travel throughout the body; arrive at site of infection via adjacent tissues or from blood

Question 38

Which are the immediate phagocytic responders?

Answer 38

Neutrophils Eosinophils Fixed macrophages

Question 39

What is the classical pathway of complement activation?

Answer 39

* The most rapid and effective pathway → works with the antibody system. * C1 binds antibodies for activation, then acts as an enzyme ultimately leading to the cleavage of C3, which splits into C3a and C3b.

Question 40

What is the lectin pathway of complement activation?

Answer 40

* Involved in the defence against bacterial infection. * Mannose-binding lectin (MBL) binds to carbohydrates present on the surface of the bacteria and becomes activated so that it can then split C3 into C3a and C3b.

Question 41

What is the alternative pathway of complement activation?

Answer 41

* Involved in the defence against bacteria, pathogens, and virally infected cells. * Properdin (in plasma) interacts with other plasma proteins leading to the splitting of C3 into C3a and C3b.

Question 42

C3 (inactive precursor) is split into C3a and C3b. Compare the two.

Answer 42

* **C3a** → diffuses away and can activate inflammatory responses (i.e., mast cell degranulation and histamine release) → acts as hormone * **C3b** → binds to bacterial surface and enhances phagocytosis → does NOT act as hormone

Question 43

Complement consists of carbohydrates that interact. True or False?

Answer 43

False. Complement consists of proteins that interact.

Question 44

Complement consists of proteins that interact with each other. True or False?

Answer 44

True.

Question 45

There is only one possible pathway for complement activation. True or False?

Answer 45

False. There are three pathways.

Question 46

The complementary pathway is a pathway for complement activation. True or False?

Answer 46

False. The three pathways are alternative, lectin, and classical.

Question 47

C3 is an active precursor that splits into the inactive C3a and C3b. True or False?

Answer 47

False. C3 is an inactive precursor that splits into the active C3a (acts as hormone) and C3b (opsonizes) components.

Question 48

C3b inhibits phagocytosis. True or False?

Answer 48

False. C3b enhances phagocytosis.

Question 49

Complement can form a membrane attack complex that pokes holes in the plasma membrane of bacteria. True or False?

Answer 49

True.

Question 50

What are interferons? Give 2 examples.

Answer 50

* A major class of cytokines released by activated lymphocytes, macrophages, and virally infected cells. * They bind receptors on normal cells to trigger an antiviral response * **IFN-alpha** → produced by virally infected cells; stimulates NK cells * **IFN-gamma** → produced by T-cells and NK-cells and stimulates macrophages

Question 51

What are interleukins? Give 2 examples.

Answer 51

* A major class of cytokines that are released by all types of WBCs that allow for coordinated immune responses. * **IL-1** → produced by innate immune cells and induces fevers * **IL-2** → produced by many immune cells and promotes inflammation.

Question 52

What are tumour necrosis factors? Give an example.

Answer 52

* A major class of cytokines that are released by many immune cells and can help the body destroy cancer cells. * **TNF-alpha** → released by macrophages and lymphocytes and can induce tumour cell death.

Question 53

What are the 7 functions of mast cells?

Answer 53

1. Increases blood flow 2. Activates macrophages 3. Increases capillary permeability 4. Activates complement 5. Stimulates regional clotting reaction 6. Increases regional temperature 7. Activates adaptive defences

Question 54

Compare and contrast the functions of MHC Class I and MHC Class II proteins and describe their distribution among bodily cells.

Answer 54

**Class 1** → expressed on surface of nucleated cells (e.g., NOT RBCs); useful in response against **intracellular** threats; CD8+ T-cells respond to antigens presented on class I MHC. **Class 2** → expressed on specialized antigen presenting cells; useful in response against **extracellular** threats; CD4+T-Cells respond to antigens presented on class II MHC

Question 55

Identify the major components of antibodies.

Answer 55

* Two parallel polypeptides; a pair of heavy chains and a pair of light chains, each with a constant region and a variable region * Variable regions have antigen-binding sites that confer specificity for an antibody * Binding sites within the constant region can activate complement (e.g., part of the classical complement pathway)

Question 56

What happens during an acute bacterial infection?

Answer 56

1. Physical defences are breached. 2. **Immediate phase** → resident macrophages recognize and begin to phagocytose threats and secrete signals (e.g., cytokines) to recruit more immune cells. 3. **Induced phase** → circulating cells leave blood vessels and enter tissues → dendritic cells goes to lymph to activate adaptive response 4. Activation of adaptive immune system → dendritic cells present antigen to T- and B-cells.

Question 57

What is the primary cell utilized by the innate immune system to alert and activate the adaptive immune responses?

Answer 57

Dendritic cells

Question 58

Describe characteristics of adaptive immunity.

Answer 58

* **Specificity** → results from activation of specific lymphocytes; each T/B cell has receptors specific for one antigen but ignores others * **Memory** → division of activated lymphocytes leads to an effector cell and a memory cell * **Versatility** → results from large diversity of lymphocytes * **Tolerance** → cells do not target ‘self’ tissues

Question 59

Describe the activation of CD8+T-Cells.

Answer 59

* They become activated when they recognize antigens bound to class I MHC proteins. * Full activation requires further signals in the form of co-stimulation * Activated CD8+T-Cells acquire one of three identities: * Cytotoxic T-cells → directly kill target cells * Memory cytotoxic T-cells → remain inactive in prep for next infection * Regulatory T-cells → dampen response to prevent autoimmunity

Question 60

Describe the activation of CD4+ T-Cells.

Answer 60

* They become activated when they recognize antigens bound to class II MHC proteins. * Full activation requires co-stimulation * Gives rise to * Activated helper T-cells → help B-cells to secrete antibodies * Memory helper T-cells

Question 61

Dendritic cells connect the innate and adaptive immune responses. True or False?

Answer 61

True.

Question 62

Major Histocompatability complex proteins can display lipids to T-cells. True or False?

Answer 62

False. They display peptides.

Question 63

MHC class I can bind to TCRs on CD4+T-cells. True or False?

Answer 63

False. MHC Class II can bind to TCRs on CD4+T-cells.

Question 64

MHC Class I can bind to TCRs on CD8+Tcells. True or False

Answer 64

True.

Question 65

Red blood cells express MHC Class I. True or False?

Answer 65

False. RBCs are not nucleated, and MHC class I only presents on nucleated cells.

Question 66

MHC Class II is expressed on all nucleated cells. True or False?

Answer 66

False. MHC Class II is expressed on antigen presenting cells.

Question 67

MHC Class II can present antigens derived from extracellular bacterium. True or False?

Answer 67

True.

Question 68

Co-stimulation is required for T-cell activation. True or False?

Answer 68

True.

Question 69

Describe B-cell sensitization.

Answer 69

When a BCR encounters a specific antigen, it prepares for activation → antigens are internalized and displayed on MHC class II proteins. The B-cell is now ready for activation via T-cell ‘help’

Question 70

Describe B-cell activation.

Answer 70

* After sensitization, a B-cell must encounter a helper T-Cell that was exposed to the _same_ antigen * This T-cell will bind the antigen presented on the class II MHC complex of the sensitized B -cell * The T-cell will then secrete cytokines to activate the B-cell

Question 71

What are the functions of activated B-cells?

Answer 71

* Memory B-cells → long-lived; react to the same antigens; secondary exposure leads to secretion of lots of antibodies * Plasma cells → antibody ‘factories’

Question 72

Describe the mechanisms of action of antibodies. [7]

Answer 72

* Neutralization * Precipitation and agglutination * Prevention of pathogen adhesion * Stimulation of inflammation * Attraction of phagocytes * Opsonization * Activation of complement

Question 73

Describe the 5 classes of immunoglobulins.

Answer 73

* **IgG** → most abundant * **IgE** → involved in allergies * **IgD** → BCR; crucial in B-cell sensitization * **IgM** → pentamer; first class secreted once a B-cell is activated * **IgA** → in secretions (e.g., mucous, semen, saliva)

Question 74

Describe the primary antibody response.

Answer 74

* Involves B-Cell activation * IgM secreted first, then replaced by IgG * Takes ~1 week for titre to peak.

Question 75

Describe the secondary antibody response.

Answer 75

* Activation of memory B-cells * More powerful response than primary * Faster rise in titres * Predominantly IgG

Question 76

The 5 types of immunoglobulins are IgA, IgD, IgE, IgF, and IgG. True or False?

Answer 76

False. Ig-GAMED No IgF

Question 77

An immunoglobulin consists of a heavy chain and a light chain. True or False?

Answer 77

False. An immunoglobulin consists of a pair of heavy chains and a pair of light chains connected by a disulfide bond, not just one of each.

Question 78

Each chain of an immunoglobulin contains a constant region and a variable region. True or False?

Answer 78

True.

Question 79

An immunoglobulin directly leads to the perforation of a bacterium via complement. True or False?

Answer 79

False. This occurs indirectly through the classical pathway of complement activation.

Question 80

The first immunoglobulin secreted into the blood in response to an infection are IgM and IgG. True or False?

Answer 80

True.

Question 81

The IgG spike is higher than the IgM spike during a secondary infection. True or False?

Answer 81

True.

Question 82

What cells are CD4+?

Answer 82

T-helper cells

Question 83

Which aspects of the adaptive immune responses are affected by a deficiency in CD4+ cells?

Answer 83

B-cell activation

Question 84

What is the function of the thymus? What type of organ is it?

Answer 84

* The thymus is a primary lymphoid organ. The thymus is particularly important for the maturation of T-lymphocytes.

Question 85

What is the function of the thymus? What type of organ is it?

Answer 85

* The thymus is a primary lymphoid organ. The thymus is particularly important for the maturation of T-lymphocytes.

Question 86

DiGeorge Syndrome is a primary immunodeficiency disease that is characterized by an absent or poorly-developed thymus leading to deficient T-cell production. Why do you think someone with this syndrome is susceptible to infection?

Answer 86

Because they do not have a completely functioning immune system because they won't have Natural Killer T cells for cell-mediated immunity or helper T cells for antibody-mediated immunity.

Question 87

DiGeorge Syndrome is a primary immunodeficiency disease that is characterized by an absent or poorly-developed thymus leading to deficient T-cell production. Certain populations of T-cells can participate in the antibody response. Identify this population T-cells and predict how DGS would affect their function and effects on the antibody response.

Answer 87

Helper T cells. If Helper T is not functioning, then you do not have B cell activation which means that you do not have antibody mechanisms occurring during antibody-mediated immunity. Also would prevent the classical complement pathway and lower perforin, phagocytosis etc.

Question 88

How would low levels of PTH affect circulating ion concentrations?

Answer 88

Low PTH = (generally occurs when you have high Ca2+ in blood) → decreased reabsorption of Ca2+ in kidneys (more Ca2+ excreted in urine) and lesser breakdown of bones to release Ca2+. This would also contribute to very low circulating Ca2+ ions.

Question 89

Define five general functions that occur in the digestive system and provide at least two examples of each function.

Answer 89

* **Propulsion** → peristalsis; segmentation * **Digestion** → physical like chewing; chemical like HCl, salivary amylase, lingual lipase * **Absorption** → * **Coordination** → taste cells; salivary reflexes, gag reflex, gastric reflex * **Protection** → mucous membranes

Question 90

Describe the organization of the digestive tract wall, including the four main layers, the location of the neural plexuses.

Answer 90

* **Submucosal plexus** → contains visceral sensory, parasympathetic and sympathetic postganglionic neurons * **Myenteric plexus** → contains ENS neurons (interneurons and motor neurons)

Question 91

Describe the movements occurring the the segmentation and peristalsis.

Answer 91

* **Peristalsis** → spreading waves of contraction in the circular layer * **Segmentation** → rhythmic cycles of contraction that fragment the food but do not produce forward movement

Question 92

Compare and contrast the accessory organs of oral cavity in terms of tissue composition and function.

Answer 92

* **Teeth** → tooth pulp contains blood vessels and nerves; enamel is crystallized calcium phosphate; helps with physical digestion * **Tongue** → skeletal muscle; mobility enhanced by extrinsic muscles; helps with digestion of fats (lingual lipase); physical digestion and propulsion; taste (via papillae which contain taste buds which contain taste receptor cells) * Signalling of taste receptors through afferent neurons can trigger a variety of reflexes (saliva, gag, gastric)

Question 93

Explain the events that occur in each of thee phases of swallowing reflex.

Answer 93

There are **three phases of swallowing**, which is initiated with a voluntary act, then proceed through a precise series of muscle reflexes mediated by the CNS (buccal and pharyngeal) and ENS (lower esophageal). * **The buccal phase** → voluntary; tongue elevates, pushing bolus against hard palate, tongue retracts, forcing bolus into oropharynx * **Pharyngeal phase** → reflexive triggered in response to mechanoreceptor activation; peristaltic contraction of pharyngeal muscles; epiglottis closes over trachea; muscles of soft palate blocks nasopharynx * **Esophageal phase** → neural activity in the myenteric plexus coordinates the contraction wave; at the distal end of esophagus, stretch receptors trigger relaxation of the smooth muscle in the lower esophageal sphincter → allows movement into stomach

Question 94

Compare and contrast the neural control of salivating and swallowing.

Answer 94

* Saliva is continually secreted into the digestive tract. * **Both divisions of the ANS** innervate salivary glands. Parasympathetic activity **enhances** the rate of secretion, while sympathetic activity **inhibits** it. * Activation of **chemoreceptors** (taste cells) and **mechanoreceptors** in the oral cavity **trigger** **salivary reflexes** via long reflexes which are **integrated in** the **medulla**. * Both involve the activation of mechanoreceptors. * Both involve the activation of reflexes * Salivating involves the activation of mechanoreceptors and chemoreceptors. * Salivating uses mostly ANS while swallowing uses both ANS and SNS. * Swallowing involves the contraction and relaxation of muscles.

Question 95

Explain why peristalsis can move a bolus in one direction and why segmentation does not.

Answer 95

* Segmentation occurs in both directions allowing for more efficient mixture and digestion of food.

Question 96

One division of the ANS enhances peristalsis and segmentation, the other inhibits it. Which is which?

Answer 96

Parasympathetic division enhances; sympathetic division inhibits.

Question 97

Would you expect excitatory or inhibitory subtype of muscarinic receptors on gastrointestinal smooth muscle?

Answer 97

Excitatory

Question 98

Describe the organization of the muscle fibres in the sublayers.

Answer 98

* Outermost longitudinal layer → myocytes arranged along the length of the tube * Circular layer → myocytes are arranged around the circumference of the tube. * Connected via gap junctions and influenced by pacesetter cells which create regular rhythms of depolarization and repolarization which can spread throughout the muscle layer.

Question 99

Describe the activation of taste cells on the tongue.

Answer 99

* Signalling of taste receptors through afferent neurons can trigger a variety of reflexes (saliva, gag, gastric) * Activation of these chemoreceptors and mechanoreceptors in the oral cavity trigger salivatory reflexes via long reflexes which are integrated in the medulla.

Question 100

Describe how a non-food related cue can trigger saliva production. What is the benefit of this type of behavioural control?

Answer 100

* Recall Pavlov's dogs. * Having saliva ready for when food is ready so that digestive system is primed and ready to go → form of allostasis!

Question 101

Does the esophagus contribute to any of the other functions of the digestive system besides propulsion?

Answer 101

* **Protection** → stratified squamous epithelia which is a physical barrier to prevent abrasion and protect underlying tissue from pathogen * **Coordination** → stretch receptors in the lower esophagus trigger relaxation of smooth muscle in cardiac sphincter to allow passage of bolus into stomach.

Question 102

What is the purpose of taste buds in the pharynx?

Answer 102

* To detect foul food and trigger gag reflexes before allowing passage into esophagus. * Also, feedforward reflexes that ‘warn’ the stomach about incoming food, allowing it to get a jump on appropriate secretions and digestive movements.

Question 103

Describe the organization and function of the structures of the stomach and stomach wall, including the sphincters, muscle layers, rugae, gastric glands, and gastric pits.

Answer 103

* Temporary storage of food and liquid. * Secretion of gastric juice → chemical digestion * Destruction of pathogens → protection * Secretes hormones → coordination * Churning movements of smooth muscle layers → physical digestion * Rugae → allow stretching of stomach, sensed by stretch receptors in stomach wall * Pits → lined by mucous-secreting epithelial cells; protection against harsh acidity of lumen * Glands → deep to the pits; produce a variety of secretions

Question 104

Compare and contrast the secretions of parietal cells, chief cells, and G cells.

Answer 104

**Parietal cells** → secrete water and intrinsic factor as well as H+ and Cl- **Chief cells** → secrete zymogen pepsinogen which is cleaved by acidic environment to pepsin. **G cells** → secrete gastrin into bloodstream and underlying tissue _not_ lumen of stomach, a peptide hormone; signals metabotropic receptors which act in local reflexes as a paracrine factor, enhancing the activity of parietal and chief cells. (= negative feedback loop → pH rises → triggers gastrin release → enhances secretion of acid → lowers pH → stops signal to secrete gastrin)

Question 105

Describe and classify the key processes occurring within parietal cells that are involved in the secretion of stomach acid (i.e., enzyme activity and membrane transport).

Answer 105

* CO₂ and H₂O combine to form H₂CO₃ * H₂CO₃ dissociates into H⁺ and HCO₃^- ions * H⁺ is pumped from the parietal cell to the lumen using H⁺/K⁺ ATPase * HCO₃^- moves from the parietal cell to the interstitial fluid and Cl^- from the interstitial fluid enter the parietal cell via the Cl^-/HCO₃^- exchanger (i.e., an antiport) * Cl^- then diffuses from the parietal cell to the lumen via chloride leak channels down its concentration gradient. * In the lumen Cl^- and H⁺ combine to form HCl.

Question 106

Explain the effects of gastrin on the secretions of cells within gastric pits and the muscularis layer of the stomach.

Answer 106

**G cells secrete gastrin** that acts in local reflexes as a **paracrine factor**, enhancing the activity of **chief cells** (secretion of pepsinogen) and **parietal cells** (secretion of HCl).

Question 107

Discuss the reflexes triggered in the cephalic phase in terms of stimuli and effects on stomach secretion and motility.

Answer 107

* In the cephalic phase, the CNS stimulates and enhances gastric secretion in preparation for receiving food. * The brain can initiate or enhance the rate of all gastric secretions via the vagus nerve (parasympathetic), which innervates the submucosal plexus in the stomach. * Chemo- or mechano-receptor activity in the oral cavity, pharynx, and esophagus enhance vagal activity. * Gastric secretions are also regulated by the brain's circadian clock (i.e., enhanced before expected meal time)

Question 108

Describe how parietal cells secrete HCl into the gastric lumen.

Answer 108

* Parietal cells have high levels of carbonic anhydrase, which generates free H+. * Proton pumps (i.e., an ATPase) perform active transport of the H+ against its concentration gradient into the lumen. * Secondary active transport exchangers increase the concentration of chloride inside the parietal cells, and then the chloride will diffuse down its concentration gradient through leak channels (i.e., facilitated diffusion) into the lumen of the gastric gland.

Question 109

The oblique layer of the stomach is closer to the lumen than the circular layer. True or False?

Answer 109

True.

Question 110

Gastric pits are deep to gastric glands and are found within the submucosal layer of the stomach. True or False?

Answer 110

False. Gastric glands are deep to gastric pits and they are all found within the mucosal layer.

Question 111

Parietal cells secrete IF, hydrogen ions, chloride ions, and water. True or False?

Answer 111

True.

Question 112

Chief cells secrete pepsin, which is activated by gastrin. True or False?

Answer 112

False. Chief cells secrete pepsinogen, which is activated by the low pH of the stomach.

Question 113

G cells are exocrine cells which secrete gastrin. True or False?

Answer 113

False. Exocrine glands secrete into the lumen, but G cells secrete gastrin into the tissue, which makes them endocrine cells.

Question 114

Discuss the reflexes triggered in the gastric phase in terms of stimuli and effects on stomach secretion and motility.

Answer 114

* Local (cells in stomach), neural (sensory and mechanoreceptors), hormonal (gastrin) * Mixing waves and gastric secretion are enhanced by both gastrin and neural reflexes which send signals to the submucosal and myenteric plexus → enhance secretions. * Stomach stretching and the release of gastrin stimulate feedforward short reflexes that accelerate activity further down the GI tract. * Stomach filling induces relaxation of ileocolic sphincter and increased colonic propulsive activity.

Question 115

Discuss the reflexes triggered in the cephalic, gastric, and intestinal phase in terms of stimuli and effects on stomach secretion and motility.

Answer 115

* Refers to events driven by changes detected within the lumen of the duodenum by local sensory receptors (chemo-, mechano-) * Mixing waves and gastric secretions are both inhibited by intestinal hormones and duodenal neural reflexes. * In general these act to inhibit the secretions and motility of the stomach to slow down the rate of gastric emptying and reduce the influx of chyme into the small intestine.

Question 116

Activating stretch receptors in the stomach wall increases secretion from gastric glands and enhances contractions of smooth muscle layers. Explain why this makes adaptive sense.

Answer 116

* Lack of physical and chemical digestion in the stomach translates to less efficient absorption farther along in the gastrointestinal tract. * These reflexes ensure that digestion occurs when food is present, but not when food is not present. * Digestion is not necessary all the time, so these reflexes protect the stomach lining by ensuring no acid secretion when there is no food to digest, and conserve ATP by preventing smooth muscle contraction.

Question 117

What is the benefit to the body of having both neural and endocrine reflexes occurring simultaneously and acting on the same general targets?

Answer 117

By having both, the response can be both fast and maintained over several hours.

Question 118

Why does greasy food work to stop a hang-over but drinking water to remedy dehydration does not?

Answer 118

* Filling the stomach with liquid will stimulate acid production, and the high acid environment can cause the nausea. * Adding food to the stomach can help ‘quench’ the acid. * Also, introducing fat into the duodenum stimulates the secretion of CCK, which initiates the intestinal phase, which tells the muscle layer of the stomach to stop churning, thereby reducing nausea.

Question 119

Identify the components of the lower digestive tract in the correct order, including all their sphincters, and indicate where accessory organs connect to the primary GI tract.

Answer 119

* Pyloric sphincter * Small intestine → duodenum, jejunum, ileum * Ileocecal sphincter * Large intestine → ascending, transverse, descending * Rectum * Anal sphincter Accessory * Appendix (attached to bottom of ascending colon) * Liver (beside stomach) * Gallbladder * Pancreas

Question 120

Compare and contrast the organization (and functions) of the different parts of the small and large intestine, including how these structures of muscle layers, mucosa, and immune specialization relate to their function.

Answer 120

* The **small intestine** has a complete longitudinal muscle layer → both peristalsis and segmentation occur * Produces more secretions than large intestine. * Most absorption occurs in the small intestine, especially the jejunum. * Circular folds are covered in villi * The **large intestine** only contains bands of longitudinal muscle → peristalsis and compaction occur. * More MALT is associated with the large intestine (e.g., the appendix) * Absorbs few nutrients, but does absorb some vitamins (especially in proximal sections) and water (especially in distal regions)

Question 121

Give at least one example of a short (ENS-mediated) reflex that is driven by the lower digestive tract, and one that affects it.

Answer 121

Chyme in the duodenum **inhibits the release of gastrin** and **inhibits the churning of the stomach (slow down the rate of gastric emptying)**.

Question 122

Identify at least two hormones secreted by the organs of the lower digestive tract and analyze their pathways for secretion and effects on target organs.

Answer 122

**Cholecystokinin** is a **peptide hormone** released by the **duodenum** that controls the release of **bile** and **pancreatic juice**. * The liver secretes bile continuously. * **CCK** triggers the **contraction of the gallbladder**, emptying the stored bile. * **CCK** triggers the **relaxation of the** hepatopancreatic sphincter (**duodenal papilla**), allowing the bile and pancreatic secretions to reach the digestive tract. * **Bile** breaks down lipid droplets by emulsification. **Sensor**: released in response to fatty or peptide rich chyme in the duodenum. **Effectors**: gallbladder and duodenal papilla **Cholecystokinin** also influences the endocrine functions of **the pancreas** in a **feedforward reflex**. * **CCK** in the bloodstream can also act on the endocrine cells within the pancreas to **enhance** **the secretion of insulin**. * This pathway allows **insulin levels to rise** **in preparation** for the **glucose** that is soon to be absorbed by the intestine. **Sensor**: glucose receptor in digestive tract. **Effectors**: pancreas **GIP** → Chyme in duodenum → secretion of GIP → inhibits gastrin → **reduces acid secretion by parietal cell** and **reduce the motility of the gastric (stomach)** **VIP →** chyme in duodenum → secretion of VIP → dilation of intestinal capillaries → facilitates nutrient absorption

Question 123

Describe the specializations in the epithelium and muscle layers of the rectum and anal canal, including the external anal sphincter.

Answer 123

* **Rectum (simple columnar) → Anal canal (stratified squamous) → Anus (keratinized stratified squamous)** * The lining of the anal canal is subjected to **higher physical pressures** (abrasion) than the rest of the lower digestive tract. * The opening at the anal canal is controlled by a **dual sphincter** – **_an internal, smooth muscle**_ component and _**an external ring of skeletal muscle_**. **Both sphincters are contracted except during defecation.**

Question 124

Describe how the two anal sphincters are innervated and make simple predictions about how spinal cord damage will affect how these function in defecation.

Answer 124

* Relaxation of the internal anal sphincter involves two reflex arcs * Short → ENS * Long → CNS is involved via spinal cord ANS neurons * External anal sphincter is innervated by somatic motor neurons, whose activity can be controlled by descending axons that come from the primary motor cortex.

Question 125

The small intestine is ‘small’ because of its length. True or False?

Answer 125

False It is small because of its diameter.

Question 126

The large intestine is ‘large’ because of its diameter. True or False?

Answer 126

True.

Question 127

There is a sphincter between the large intestine and the rectum. True or False?

Answer 127

False.

Question 128

Liver and pancreatic secretions reach the digestive tract through the bloodstream. True or False?

Answer 128

False Liver and pancreatic digestive secretions are exocrine.

Question 129

The appendix is critical for a normal life. True or False?

Answer 129

False.

Question 130

How does loss of water through the digestive tract lead to circulatory collapse and death?

Answer 130

* Increasing the secretion of ions by enterocytes leads to water loss because it changes the concentration gradient. * A higher concentration of ions in the lumen means that water will move into by osmosis to balance the osmolarity, increasing water loss. * Increased intestinal secretion rate leads to diarrhea because there is so much water in the digestive tract that cannot be absorbed quickly enough by the large intestine. * Not enough water reabsorption leads to watery stool (i.e., diarrhea). * Diarrhea leads to dehydration because water is continually leaving the enterocytes, and water from the interstitial fluid is continually flowing into the enterocytes to replenish them. * The interstitial fluid replenishes its water content via filtration from the capillaries. * Water flows from capillaries to ISF to enterocytes to the lumen of the intestines, and then excreted from the body as diarrhea, which leads to overall body dehydration. * Blood volume will decrease, and blood pressure will decrease as well. * Loss of water through the digestive tract leads to circulatory collapse and death because reduced blood volume decreases venous return, thereby decreasing stroke volume. * Reduced stroke volume leads to lower cardiac output and reduced ability to deliver oxygen to tissues, which triggers compensatory reflexes that will attempt to elevate central blood pressure and oxygenation to keep the heart pumping. * The heart is also working harder and not receiving enough oxygen supply, which leads to damage and circulatory collapse. * Beyond a certain point, these feedback cycles lead to death.

Question 131

Describe a distinctive structural feature of the mucosa of the large intestine and explain how it contributes to the specialization for a particular function.

Answer 131

MALT in the mucosal layer of the lamina propria which is there because of the large number of bacteria in the lumen. MALT is full of immune cells that will help control and manage the bacterial population through secretion of antibodies and cytokines.

Question 132

Describe a structural adaptation you’d be more likely to see in duodenal epithelium than jejunal – and explain why it would be more common in the duodenum.

Answer 132

Duodenal glands which secrete alkaline fluid to help neutralize the acidic chyme coming from the stomach.

Question 133

Describe a structural adaptation you’d be more likely to see in jejunum’s epithelium than the duodenum – and explain why it would be more common in the jejunum.

Answer 133

The jejunum has more circular folds, villi, and microvilli which help increase the surface area and therefore its ability for absorption.

Question 134

Explain why chemical digestion is necessary for efficient and effective absorption of nutrients and why digestive enzymes are usually secreted in the form of zymogens.

Answer 134

* Absorption requires the **uptake of molecules across the plasma membranes** of **mucosal epithelial cells.** ***_The plasma membrane of mucosal epithelial cells is selectively permeable to small molecules._*** * **Large molecules** are only transportable through **(energy intensive) endocytosis**, so efficient absorption relies on **chemical digestion.** * Enzymatic (chemical) digestion leads to the break-down of macromolecules into their component parts. * **Many digestive enzymes are secreted as zymogens (inactive precursors) so that they do not digest the cell that synthesized them.**

Question 135

Identify the classes of enzymes responsible for the digestion of the four major groups of macromolecules, and give at least two specific examples of individual enzymes, including how it becomes active.

Answer 135

* Nucleases * Peptidases (e.g., pepsin) * Carbohydrases (e.g., salivary amylase) * Lipases (e.g., lingual lipase) **Pepsinogen is cleaved to reveal its active site to become pepsin** **Enzymes from the duodenum converts trypsinogen to trypsin**

Question 136

Describe the basic structure of bile salts and explain the role(s) they play in the digestion and absorption of fats.

Answer 136

* **Bile** secreted from the liver **contains** **bile salts**, which are **critical for emulsification of lipids** and thus their digestion and absorption. * **These amphipathic molecules (bile salts) can** **bind to** **fat globules and form micelles.** * **Micelles** allow **lipases** to access triglycerides to break them into **free fatty acids.**

Question 137

Compare and contrast the physiological processes involved in fat absorption across enterocytes (both membranes and intracellular events) with the equivalent processes occurring for monosaccharides and amino acids.

Answer 137

**Lipids** * Fatty acids **diffuse directly** from the lumen across the apical membrane into enterocytes * Inside the enterocytes, **fatty acids** combine with **proteins** to form **chylomicron**. * **Chylomicrons** (chyle) then **diffuse** through the **basolateral membrane** via **the** **_lymphatic system_** into **the bloodstream**. **Glucose and amino acids** * Monosaccharides (sugars) are absorbed from the **lumen into enterocytes** via either **facilitated diffusion** or **cotransport with sodium ions**. * Glucose then uses **facilitated diffusion via transporters** to enter the **blood capillaries** Glucose drains into the **hepatic portal vein** and into **the liver.**

Question 138

Compare and contrast the transport of fats, saccharides, and amino acids from intestines to the systematic circulations.

Answer 138

Question 139

Identify the major ways water, minerals, and vitamins can be absorbed across intestinal lumens.

Answer 139

* Water typically crosses the intestinal mucosa because of **osmotic gradients** due to the **movement of ions and solutes**. (flow to low) * Absorption of minerals (i.e. ions) occurs through a mix of **primary and secondary active transport**, and is **regulated by several hormones.** * Aldosterone - Na+ uptake / Na+ retention * PTH and Calcitriol - Ca2+ uptake * **These hormones** often **work by** **altering** the density of **specific transport enzymes** in enterocyte membranes. * The mechanisms for vitamin absorption depend on their chemical composition and size * **Vitamin E Lipid soluble**: transported via **micelles and chylomicrons** * **Vitamin C (Water soluble and small)** - uptake via **facilitated diffusion** * **Vitamin B12 (Water Soluble but large)** - requires **endocytosis** mediated by a protein cofactor

Question 140

Define the terms ‘absorptive state’ and ‘post-absorptive state' and explain the major features of metabolism in each state.

Answer 140

**Absorptive** → occurs when ingested food begins to be absorbed → primary hormone = insulin which promotes storage of lipids and use of glucose for ATP generation **Post-absorptive** → occurs when internal energy stores must be used for ATP generation → hormones include glucagon, epinephrine, and glucocorticoids which promote gluconeogenesis, lipolysis, and use of fatty acids for ATP generation

Question 141

Segmentation is a form of chemical digestion. True or False?

Answer 141

False. Segmentation is a form of physical digestion.

Question 142

Peptides are made from many nucleic acids. True or False?

Answer 142

False. Peptides are made from many amino acids.

Question 143

Trypsin is a zymogen secreted by the pancreas. True or False?

Answer 143

False. Trypsinogen is a zymogen secreted by the pancreas.

Question 144

Brush border enzymes are found on the basolateral surface of enzymes. True or False?

Answer 144

False. Brush border enzymes are found on the apical surface of enterocytes.

Question 145

Bile salts are zymogens secreted by the liver that interact with ingested lipids. True or False?

Answer 145

False. Bile salts are cholesterol derivatives secreted by the liver that interact with ingested lipids.

Question 146

Describe the role of trypsinogen.

Answer 146

* Trypsinogen is secreted by the pancreas into the duodenal lumen. * Enzymes present convert it to trypsin. * Trypsin then catalyzes the conversion of most other zymogens to their active form * Alpha-amylase * Lipase * Nucleases * Proteolytic enzymes

Question 147

Describe key features of the gross anatomy and histology of the liver, including the organization of blood vessels and bile ducts, lobules, and sinusoids.

Answer 147

* Most absorbed substances pass through the liver before they reach the general circulation. * It is attached to the diaphragm by the peritoneum and anchored to the stomach by the mesentary. * Folds of the mesentary also form the hepatic ligaments and divide the liver into lobes. * In addition to fenestrations, sinusoids have large gaps between adjacent endothelial cells and the underlying basement membrane.

Question 148

Discuss how rare or unique features of liver anatomy relate to the many functions of the liver.

Answer 148

* The hepatic portal vein system collects blood from organs within the abdominal cavity. * Highly vascularized → hepatocytes are organized into sheets of cells with sinusoids (capillaries) on either side * Liver sinusoids also are home to a special resident population of phagocytic macrophages

Question 149

Identify examples of liver functions in digestion, molecular storage, nutrient synthesis, and detoxification.

Answer 149

* The liver secretes bile, important for fat digestion and absorption. * The liver has a key role in glucose processing and storage in the absorptive state. * The liver acts as a store for certain key minerals and vitamins * The liver is responsible for gluconeogenesis in the post-absorptive state. * The liver is responsible for detoxification of alcohol and other drugs/toxins. * Blood storage.

Question 150

Define the terms absorptive and post-absorptive state and explain the role(s) of the liver in each state.

Answer 150

* The liver has a key role in glucose processing and storage in the absorptive state. * The liver is responsible for gluconeogenesis in the post-absorptive state.

Question 151

Identify examples of non-metabolic roles of the liver that support the function of other organ systems (beyond the digestive system).

Answer 151

* Storage of blood → liver receives 25% of CO at rest. Venoconstriction can increase venous return during exercise or in situations of reduced blood volume * Synthesis of most soluble proteins found in plasma * Liver macrophages play an important role in recycling RBCs * The liver is a secondary endocrine organ which secretes at least four hormones or prohormones * Anterior pituitary → GH → somatomedin liver → stimulate growth * Angiotensin → increase blood volume and pressure * Thrombopoietin → stimulates platelet formation * Hepcidin → important for iron homeostasis * The liver also contributes to activation or inactivation of steroid hormones produced by other endocrine organs (i.e., liver performs the first hydroxylation step of vitamin D to calcidiol, which is later converted to the active form calcitriol by the kidney)

Question 152

The liver is a large, retroperitoneal, primary digestive organ. True or False?

Answer 152

False. The liver is a large, intraperitoneal, accessory digestive organ.

Question 153

Both hepatic arteries and hepatic portal veins are afferent vessels (from the perspective of the liver). True or False?

Answer 153

True.

Question 154

Blood flows into a liver lobule at the central vein, and out through the portal triad. True or False?

Answer 154

False. Blood flows into the liver lobule at the portal triad, and out through the central vein.

Question 155

The presence of macrophages within sinusoids suggests that the liver functions like a lymphoid organ. True or False?

Answer 155

False. A lymphoid organ is defined by presence of lymphocytes, and macrophages are not lymphocytes.

Question 156

The structure of sinusoids suggests that large molecules are going to be moving in and out of capillaries at the liver. True or False?

Answer 156

True.

Question 157

Which nutrients does the liver store? [4]

Answer 157

Vitamin A Vitamin B12 Copper Iron

Question 158

What role does the liver play in the post-absorptive state?

Answer 158

Gluconeogenesis (making new glucose, and/or ketones if glucose fasting is prolonged)

Question 159

Which organ system depends the most on the liver performing its role during the post-absorptive state?

Answer 159

The CNS (i.e., the brain!)

Question 160

Describe the role the liver plays in processing alcohol.

Answer 160

Breaking down alcohol, detoxifying it.

Question 161

Why can the liver not detoxify and perform gluconeogenesis at once?

Answer 161

Some of the enzymes in both pathways use the same cofactors. The enzymes that break down alcohol and the enzymes that synthesize glucose use the same cofactors. The cofactors will be used for alcohol processing above all other functions.

Question 162

What ‘quirk’ of the liver can be exploited to treat someone for methanol poisoning?

Answer 162

The fact that cofactors in the liver will be used to process ethanol above all other functions. Methanol is broken down to formaldehyde which poisons the liver. If you add ethanol, the liver will preferentially process the ethanol, thereby halting formaldehyde production.

Question 163

What is one function of the liver that relates to the integument?

Answer 163

Vitamin D activation 1st hydroxylation step occurs in the liver (i.e., calcidiol production)

Question 164

Classify the organs of the urinary system based on their roles in urine production, storage, and transport.

Answer 164

* The kidneys process blood from the renal arteries, generating filtrate that becomes urine as it moves through kidney tissue. * The bladder plays a key role storing urine, and also in expelling it.

Question 165

Describe four functions of the kidneys that are _not_ ‘producing urine’.

Answer 165

* Removing wastes and toxins from blood (without removing nutrients) * Regulating plasma ion concentrations * Regulating blood pH * Regulating blood volume and blood pressure

Question 166

Identify three main hormones produced by the kidneys and explain their roles in maintaining homeostasis and their target organs.

Answer 166

* **Calcitriol** regulates increased calcium intake and retention * Secreted by proximal tubule cells in response to parathyroid hormone when plasma calcium is low * Calcitriol principally acts on receptors in both the digestive tract and the kidney to promote the absorption (and reabsorption) of calcium (as well as bone resorption) * **Erythropoietin** (EPO) stimulates RBC production * Secreted by intertubular fibroblasts (EPCs) within kidney tissue in response to tissue hypoxia * EPO acts on bone marrow to enhance erythrocyte (RBC) production, leading to increased blood volume (and hematocrit). * **Renin** regulates other hormones which control (increase) blood pressure and plasma volume * Secreted by cells within the juxtaglomerular apparatus (JGA) in response to decreased pressure in kidney arterioles * Renin activates angiotensin, which ultimately increases blood pressure (through vasoconstriction) and increases blood volume (through intake and reabsorption)

Question 167

Identify the key regions of nephrons and their associated blood vessels.

Answer 167

* Glomerulus → proximal convoluted tubule → descending loop → ascending loop → distal convoluted tubule → collecting duct * Glomerulus → filters blood

Question 168

Define the term filtration.

Answer 168

* Refers to the bulk flow of water and small solutes through small pores due to hydrostatic pressure.

Question 169

Define the term reabsorption.

Answer 169

* Tubular reabsorption is the process that moves solutes and water out of the filtrate and back into the bloodstream.

Question 170

Define ‘obligatory’ and ‘facultative’ in terms of nephron function.

Answer 170

* **Obligatory** → cannot be prevented * **Facultative** → regulated by hormones (especially ADH and aldosterone)

Question 171

Explain the difference between acute and chronic renal failure and describe at least two common causes and two key symptoms.

Answer 171

* **Acute** → abrupt loss of function * **Chronic** → slow, gradual deterioration in function * Metabolic wastes, excess ions, and water will be retained. * **Causes** → problems with blood supply, damage to kidney tissue, or urinary tract obstruction (e.g., a clot in a renal artery/vein, physical damage to kidney, toxins, kidney stones) * **Symptoms** → a reduction of urine production, oedema, and fatigue

Question 172

Explain the basic principles of haemodialysis for treatment of renal failure and compare and contrast this strategy with the natural functions of blood filtration that occur in the kidney.

Answer 172

* Allows waste and excess ions to be removed from the blood. * Relies on passive diffusion across a selectively permeable membrane. * The membrane permits ions and small organic molecules to pass, but restricts movement of large molecules, especially plasma proteins. * Natural filtration in the kidney requires pressure across small pores

Question 173

Explain the role of renin.

Answer 173

* **Renin** regulates other hormones which control (increase) blood pressure and plasma volume * Secreted by cells within the juxtaglomerular apparatus (JGA) in response to decreased pressure in kidney arterioles * Renin activates angiotensin, which ultimately increases blood pressure (through vasoconstriction) and increases blood volume (through intake and reabsorption)

Question 174

Explain the role of EPO.

Answer 174

* **Erythropoietin** (EPO) stimulates RBC production * Secreted by intertubular fibroblasts (EPCs) within kidney tissue in response to tissue hypoxia * EPO acts on bone marrow to enhance erythrocyte (RBC) production, leading to increased blood volume (and hematocrit).

Question 175

Explain the role of calcitriol.

Answer 175

* **Calcitriol** regulates increased calcium intake and retention * Secreted by proximal tubule cells in response to parathyroid hormone when plasma calcium is low * Calcitriol principally acts on receptors in both the digestive tract and the kidney to promote the absorption (and reabsorption) of calcium (as well as bone resorption)

Question 176

What must occur for the bladder to empty?

Answer 176

The neurons innervating the sphincters must relax so that the two urethral sphincters dilate, and the detrusor (smooth muscle layer of the bladder) must contract.

Question 177

Which urinary disorder could be caused by issues with the innervation of the urinary sphincter muscle?

Answer 177

Incontinence → inability to store urine/leakage issues

Question 178

Which urinary disorder could be caused by a bladder stone?

Answer 178

Urinary retention → inability to fully empty bladder Increased urgency/frequency Incontinence → inability to store/leakage issues.

Question 179

Which urinary disorder could be caused by problems occurring in the kidneys?

Answer 179

Changes in urinary output → related to the volume of urine produced

Question 180

How can you tell the difference between a disorder of urinary output and a disorder of urinary retention?

Answer 180

Colour of the urine can indicate solute concentration. If the kidneys cannot produce urine (i.e., decreased output; problem in kidneys), the urine may be more yellow/concentrated. If the kidneys are producing urine but there is an issue with expelling it (i.e., retention of urine; bladder stone), the urine may be less yellow/concentrated.

Question 181

Calcitriol is a hormone produced by the kidney which also acts on the kidney. True or False?

Answer 181

True.

Question 182

Anti-diuretic hormone (ADH) is a hormone produced by the kidney which also acts on the kidney. True or False?

Answer 182

False. ADH is produced by the posterior pituitary gland but acts on the kidney.

Question 183

Erythropoietin is produced by the kidney in response to increased blood volume and regulates RBC production. True or False?

Answer 183

False. Erythropoietin is produced by the kidney in response to tissue hypoxia.

Question 184

If blood volume is decreased, secretion of both renin _and_ EPO would be enhanced. True or False?

Answer 184

True. The key stimulus that EPCs are detecting to secrete EPO is hypoxia in kidney tissue. Reductions in blood volume may cause hypoxia.

Question 185

Where does blood interact with each nephron?

Answer 185

ONLY in its glomerulus. * After the glomerulus, the filtrate flows through the lumen of the nephron, into the collecting ducts, while the remaining (unfiltered) blood flows through capillaries around the nephron.

Question 186

Why is filtration not enough on its own for kidney function?

Answer 186

Filtration is done through pressure. Water and small molecules are pushed across a semi-permeable membrane through gaps (i.e., not through like diffusion), excluding larger molecules. Glucose, for instance, is excluded from urine despite being small enough to filter through gaps in the membrane.

Question 187

Describe the anatomical organization of the glomerulus, renal corpuscle, and juxtaglomerular complex/apparatus.

Answer 187

* Glomerulus → blood vessels between the afferent and efferent arterioles * Bowman's capsule/renal corpuscle → spherical structure at the beginning of each nephron which encapsulates the glomerulus * JGA → responds to changes in arteriole pressure and the flow of filtrate in the distal parts of the nephron.

Question 188

Discuss how key features of glomerular/corpuscular anatomy contributes to the specialized physiological function of glomerular filtration.

Answer 188

* The filtration membrane is made from endothelial cells, basement membrane and the ‘feet’ of podocytes. * The tissues of glomerular capillaries and visceral layer of corpuscle for the filtration membrane * Glomerular capillaries are fenestrated with large pores * The basement membrane of the glomerular capillary is the main structure that prevents movement of large molecules. * Podocytes of the visceral layer of corpuscles wrap around the basement membrane, forming filtration slits. * Small molecules pass freely through the filtration membrane, but the movement of larger molecules is restricted.

Question 189

Define the term glomerular filtration rate.

Answer 189

The rate of filtrate production by the kidneys (reported as mL/min); may be adjusted by altering blood flow through glomerulus.

Question 190

Explain the key differences between eGFR and mGFR measures and discuss the advantages and disadvantages of using eGFR.

Answer 190

1. **Estimated (e)GFR** is typically taken from plasma levels of **key waste products secreted** by the kidneys**.** * **Creatinine** can only be excreted by the kidney. (is not broken down or secreted) * Therefore, the concentration of creatinine in blood is generally high when GFR is low, and vice versa. * **(2) Measured (m)GFR** is calculated by determining the **rate of clearance of inert substances added** into plasma. * To actually directly measure GFR, researchers infuse drugs with particular properties into a person’s blood, and then measure how rapidly the drug appears in the urine. * **Inulin** is the most common drug used – it is non-toxic, not metabolized, only excreted by the kidneys, and filtered but not reabsorbed. * **(3) Disadvantages of eGFR** - Patients with unstable creatinine concentrations (high protein diet, dehydration) * PCT (Proximal Convoluted Tubule) can secrete creatinine * Cannot be used in kids (different amount of production of creatinine) * **(4) Advantages of eGFR** - can detect kidney disease since creatinine is only excreted.

Question 191

How may glomerular NFP be calculated?

Answer 191

NFP = (GHP + CsCOP) - (CsHP + BCOP)

Question 192

Make predictions about how a change in blood flow, integrity of filtration membrane, and tubular flow affect GHP, CsHP, and BCIP and thus alter NFP.

Answer 192

* Alterations to **the glomerular capillaries or arterioles**, or to **the filtration membrane** or **fluid within the nephron** can alter the balance of the four forces, changing NFP, and thus changing glomerular filtration rate (GFR). * Pressure from the volume of **fluid** in enclosed tubes - Glomerular hydrostatic pressure **(GHP)** & Capsular hydrostatic pressure **(CsHP)** * Osmotic pressure from large (i.e. impermeable) **solutes** - Blood colloid osmotic pressure **(BCOP)** & Capsular colloid osmotic pressure **(CsCOP)** * Two examples: * a) **Constricting the efferent arteriole** will **increase** **GHP**. (glomerulus will push harder → higher pressure) * b) **Blocking the drainage of urine from the nephron** will **increase** **CsHP**. (bowman’s capsule will push harder → increase pressure → to prevent more filtrate from entering the capsule)

Question 193

Identify at least two mechanisms that the kidney can use for intrinsic regulation of GFR, and at least two extrinsic mechanisms for GFR regulation.

Answer 193

* GFR is controlled by intrinsic mechanisms by autoregulation and extrinsic regulation via the RAAS (endocrine system) and sympathetic system. * The **main sensors** for homeostatic regulation of GFR are found within the **_juxtaglomerular apparatus_**. * SENSORS: Mechano- and chemosensory cells within the **JGA** **sense** **_blood pressure**_ (via arteriolar stretch) and _**the composition**_ and _**flow rate of filtrate_** within the distal parts of the nephron. * **_Varying net glomerular filtration pressure_** → adjusting the rate of filtration → **the rate of urine production** → contributes to **the homeostasis of body fluid** (volume and composition) * The main effectors for homeostatic regulation of GFR are **_arteriolar smooth muscle within the glomerulus_**_._ * EFFECTORS: contraction/dilation of Smooth muscle within efferent arterioles. Smooth muscle within afferent arterioles. Extra/intraglomerular mesangial cells. * **_Varying net glomerular filtration pressure_** → adjusting the rate of filtration → **the rate of urine production** → contributes to **the homeostasis of body fluid** (volume and composition)

Question 194

Describe the intrinsic (local) mechanisms of kidney GFR regulation.

Answer 194

**Kidney GFR** is **_primarily_** regulated by **intrinsic (local)** mechanisms - **_Autoregulation_** Eg. (homeostasis of GFR is disturbed - decreased renal blood flow) JGA detects decreased renal blood flow → decreased filtration pressure, decreased filtrate and urine production → **contraction of intraglomerular _mesangial cells_, dilation of smooth muscles in afferent arterioles, constriction of smooth muscles in efferent arterioles** → increased glomerular pressure → (homeostasis GFR restored) increased renal blood flow The disruption is sensed by the sensor (**JGA)** which alters the activity of effectors (**mesangial cells, smooth muscle in afferent & efferent arterioles**) through **_paracrine signaling._**

Question 195

Describe the extrinsic mechanisms regulating kidney GFR.

Answer 195

**Kidney GFR** is also regulated by **extrinsic mechanisms** (**the endocrine systems and nervous systems)** In addition to coordinating local responses, the JGA also **activates** **_hormonal and neural signaling**_ which can _**amplify local changes**_ and also _**initiate changes in other organ systems_** that can affect GFR. **The RAAS** coordinates **_short-term vasoconstriction**_ and _**long-term increases in blood volume_** to help maintain renal blood flow (and thus GFR) Eg. (homeostasis of GFR is disturbed) decrease renal blood flow → decreased filtration pressure, decreased filtrate and urine production. **Endocrine System Part (angiotensin II)** JGA releases hormone (renin) into bloodstream → renin triggers formation of angiotensin I → angiotensin-converting enzyme (ACE) activates angiotensin I to angiotensin II in lungs capillaries → a) angiotensin II constricts peripheral and efferent arterioles → increased systemic blood pressure → increased glomerular pressure. b) **angiotensin II triggers adrenal glands to secrete aldosterone** → **aldosterone increases Na+ retention → water retention** → **increased blood volume** → increased systemic blood pressure → increased glomerular blood pressure **Nervous System Part (triggered by angiotensin II and efferent renal neurons)** c) angiotensin II → 1) increased stimulation of thirst centers → increased fluid consumption. 2) **increased ADH production → increased fluid retention**. 3) increased sympathetic motor tone → a) constriction of systemic veins → increased blood volume → increased systemic blood pressure → increased glomerular blood pressure b) increased cardiac output → increased systemic blood pressure → increased glomerular blood pressure. c) angiotensin II and sympathetic activation stimulates peripheral vasoconstriction → increased systemic blood pressure → increased glomerular blood pressure.

Question 196

Blood flows through a glomerulus from the efferent arteriole to the glomerular capillaries. True or False?

Answer 196

False. Blood flows through a glomerulus from the afferent arteriole to the glomerular capillaries.

Question 197

The visceral layer of the renal corpuscle consists of podocytes that attach to the capillary basement membrane. True or False?

Answer 197

True.

Question 198

A glycoprotein like HCG, which has a molecular size of 36.7kDa, cannot pass through the glomerular filtration membrane. True or False?

Answer 198

False. Molecules between 10-70kDa have some ability to pass through the membrane but are filtered less efficiently. Even if we didn’t know the size of the protein, we know that it does pass through the glomerular filtration membrane because HCG is what pregnancy tests detect in the urine for a positive result.

Question 199

Explain why constriction of the efferent arteriole will increase GHP and predict what that will mean for GFR.

Answer 199

Constriction of the efferent arteriole increases resistance and increases pressure in the glomerulus, which enhances net filtration rate.

Question 200

Explain why blockage of the nephron will increase CsHP and predict what that will mean for GFR.

Answer 200

Blocking the nephron increases pressure in the nephron, which decreases the net filtration rate.

Question 201

What would happen to these forces (and GFR) if the afferent arteriole was constricted?

Answer 201

If the afferent arteriole was constricted, less blood is entering the glomerulus, which decreases resistance and pressure in the glomerulus, which decreases NFR.

Question 202

What about if the filtration membrane is damaged? What happens to GFR?

Answer 202

More solutes would enter the glomerular filtrate, which may increase CsCOP and decrease BCOP. This increases glomerular filtration rate. Overproduction of urine is a sign of kidney failure.

Question 203

The JGA apparatus only responds to changes in the amount of blood flow through kidney arterioles. True or False?

Answer 203

False. The JGA also responds to distal tubule flow rate of filtrate.

Question 204

Kidneys contain both sensory and effector neurons. True or False?

Answer 204

True.

Question 205

Constriction of afferent arterioles will reduce glomerular hydrostatic pressure, and thus reduce GFR. True or False?

Answer 205

True.

Question 206

Constriction of blood vessels in tissues outside of the kidney will increase blood flow to the kidney and thus increase GFR. True or False?

Answer 206

True.

Question 207

Explain three general types of functions the renal tubule performs to create urine from glomerular filtrate.

Answer 207

* Remove nutrients and proteins * Reabsorb filtered fluid (water and ions) * Concentration waste products

Question 208

Describe the major functions of the proximal convoluted tubule and explain how its anatomy (including key characteristics of its epithelium) supports these functions.

Answer 208

* The only part of the nephron capable of absorbing organic substances. * Found in the renal cortex.

Question 209

Explain reabsorption of organic nutrients, such as glucose, by the PCT in terms of the general type and location of different transmembrane transporter proteins that are involved.

Answer 209

* The apical surface of PCT cells express co-transporters for sodium and glucose (or sodium and a.a.) * The basolateral surface expresses transporters for glucose (or a.a.) * The basolateral surface also expresses sodium/potassium ATP-ase pumps which maintain sodium gradients.

Question 210

Explain why paracellular water (and ion) reabsorption in the PCT occurs and predict the changes that would be seen if solute reabsorption was altered.

Answer 210

* If glucose and other small molecules are pumped out of the lumen into the PCT cells (and onto the ISF): * The osmolarity of tubular fluid will decrease, and the osmolarity of the ICF and ISF will increase. * The osmotic gradient draws water into the ISF (through the leaky tight junctions of the epithelium)

Question 211

Explain why diabetes mellitus is associated with polyuria and polydipsia.

Answer 211

* The osmolarity of tubular fluid will not remain high. * The osmotic gradient from lumen to ISF will be reduced. * Less water will be reabsorbed by the PCT epithelium and more will remain within the lumen (turning into urine). * Result = glycosuria and polyuria * Decreased water reabsorption leads to decreased blood volume which activates the RAAS (renin to angiotensin I to angiotensin II) which can also activate ADH secretion, leading to thirst.

Question 212

Explain the secretion of protons, nitrogenous wastes, and organic ions by PCT and DCT cells in terms of the general type and location of transmembrane transporter proteins and different cellular enzymes that are involved.

Question 213

Discuss why many common drugs can be nephrotoxic in large quantities or when renal function is compromised.

Answer 213

* Kidneys must temporarily store these toxic compounds to secrete them * If transport mechanisms are compromised/overwhelmed, the cells with the toxins are exposed to damage.

Question 214

Would you need passive or active transport to remove glucose from tubular fluid?

Answer 214

Glucose requires active transport because there is a higher concentration in blood plasma, so the movement is against the concentration gradient. The aim is to reduce glucose concentration in tubular fluid to zero.

Question 215

Would you need passive or active transport to secrete waste products into tubular fluid?

Answer 215

Waste products require active transport for movement against a concentration gradient. The aim is to decrease nitrogenous waste concentration in ISF and plasma to as close to zero as possible.

Question 216

What happens if filtered glucose is not all pumped out of the lumen into PCT cells (and then on into the ISF)?

Answer 216

* The osmolarity of tubular fluid will not remain high. * The osmotic gradient from lumen to ISF will be reduced. * Less water will be reabsorbed by the PCT epithelium and more will remain within the lumen (turning into urine). * Result = glycosuria and polyuria

Question 217

Albumin is secreted by PCT cells into the lumen through exocytosis. True or False?

Answer 217

False. Albumin is absorbed by PCT cells from the lumen into the cell and then into the tubular fluid.

Question 218

Protons are secreted by PCT and DCT cells primarily through counter-transport with sodium. True or False?

Answer 218

True.

Question 219

Ammonia is secreted by PCT and DCT cells primarily through co-transport with protons. True or False?

Answer 219

False. Ammonia is a nonpolar substance that can diffuse directly through the membrane. Ammonium does require co-transport.

Question 220

Organic anions can be excreted into lumen by both primary and secondary active transport. True or False?

Answer 220

True.

Question 221

Nephrotoxic drugs are more likely to cause problems in people with pre-existing renal problems and become more dangerous at lower concentrations in older patients. Explain why.

Answer 221

Renal function decreases with age.

Question 222

Nephrotoxic drugs are also often synergistic (more likely to cause damage when given together). Why does this also contribute to the increased dangers of potentially nephrotoxic drugs for older people?

Answer 222

Older people are often already taking some nephrotoxic drugs for other conditions (e.g., ACEi and SGLT-2 inhibitors for chronic heart failure).

Question 223

Describe the role of the loop of henle.

Answer 223

* Nephron segments which rely on transcellular transport, so they are more selective about which solutes (and water) can reabsorb compared to PCT. * It descends into the medulla. * There is osmolarity gradient in the medulla (deeper = higher gradient)

Question 224

Beyond the PCT all nephron segments allow paracellular transport. True or False?

Answer 224

False. Beyond the PCT, all nephron segments have tight epithelia and exhibit no paracellular transport.

Question 225

The only parts of the nephron that pass through the medulla are the limbs of the Loop of the Henle. True or False?

Answer 225

False. The CD passes through the medulla as well.

Question 226

The thin limb of the Loop of Henle is named for its small diameter. True or False?

Answer 226

False. It's named for the simple squamous epithelia.

Question 227

The DCT can be distinguished from the PCT based on its location within the kidney and its lack of microvilli. True or False?

Answer 227

False. They are both found in the kidney.

Question 228

What is counter-current/multiplication?

Answer 228

* **Counter-current** → tubular flow in the limbs of the loop of henle going in opposite directions relative to the ISF osmolarity gradient in the medulla * **Multiplication** → the arms of the loop also have different permeabilities for water and solute movement, which enhances overall reabsorption.

Question 229

The thin descending limb is permeable to solutes. True or False?

Answer 229

False. The thin descending limb is permeable to water (via aquaporin-1 on apical membranes); but impermeable to solutes. The direction of flow in this limb accelerates water reabsorption, as the osmolarity of the ISF increases the deeper the limb goes.

Question 230

The thick ascending limb can pump ions out of the tubular fluid and is permeable to water. True or False?

Answer 230

False. The thick arm is completely impermeable to water but can pump sodium and chloride out of the lumen due to the expression of the NKCC transporter on the apical surface → these ions are added to the ISF, maintaining the medulla's osmotic gradient.

Question 231

How is the osmolarity gradient in the deep medulla maintained?

Answer 231

* Partly by urea permeability in the papillary duct, located at the deepest part of the medulla, which expresses urea transporters.

Question 232

Why does a kidney have JM nephrons? What would happen if it only had corticle nephrons?

Answer 232

* JM nephrons maintain the osmolarity in the medulla so that everything else functions per normal. * Having a longer loop and exposing it to more of the gradient means you can utilize more of the counter- current multiplication. * So, the deeper the nephron extends into the medulla (where the osmolarity is strongest), the more water can be reabsorbed from the filtrate. * Cortical nephrons are limited in how much water they can reabsorb. In situations where dehydration must be avoided, JM nephrons allow better conservation of water in the body.

Question 233

There is some evidence that kidneys can control which types of nephrons are being used to make urine, depending on physiological conditions. Under what circumstances do you think a kidney would preferentially use its JM neurons?

Answer 233

The kidney may preferentially use its JM neurons when dehydrated (i.e., low body fluid; high plasma osmolarity), so the goal is conserve water to restore plasma osmolarity.

Question 234

Imagine you’re an ‘Intelligent Designer’ – how would you create a mechanism to enable the kidney to switch between two nephron types as needed?

Answer 234

Different sets of receptors (i.e., signalling proteins) in the JGA of different types of nephrons. Thus, a high plasma osmolarity will result in signals to constrict the afferent arteriole in cortical nephrons while dilating the afferent arteriole in JM nephrons, so that blood flow preferentially enters JM nephrons, (or vice versa).

Question 235

Describe facultative water and solute reabsorption in the DCT and CD.

Answer 235

* Only occurs stimulated by hormonal signals.

Question 236

What would occur without hormone signalling in the DCT and CD?

Answer 236

* The DCT and CD have little to no paracellular transport and are impermeable to water ‘at rest’ * Without hormone signalling, water would be retained in the lumen even while passing through the high osmolarity in the deep medulla. * This would lead to a large volume of dilute urine.

Question 237

Describe the role of ADH/vasopressin in the DCT and CD.

Answer 237

* ADH/vasopressin is secreted by the posterior pituitary. * It acts through AVPR2 receptors in the basolateral membrane of DCT/CD cells * This leads to the insertion of aquaporin-2 into the apical side. * Thus, when ADH is present water is reabsorbed by the DCT and CD, and urine osmolarity increases.

Question 238

Which common effects of drinking alcohol would be a direct result of inhibition of ADH secretion?

Answer 238

More frequent urination. Higher volumes of urine are produced that cannot be concentrated due to lack of ADH signalling. Dehydration will result (i.e., a hangover) due to blocked ability to conserve water, which increases plasma osmolarity. Apple juice would be more effective than pure water at resolving the dehydration (i.e., ‘curing’ a hangover) because water follows solutes. Absorption across the intestinal epithelia will be faster if solutes are included with the fluid. Apple juice has a higher solute concentration than water (obviously), so water absorption in the intestine will be enhanced.

Question 239

Predict the two main symptoms of *diabetes insipidus* and explain how you would determine whether a patient was suffering from diabetes insipidus or diabetes mellitus.

Answer 239

Excessive thirst and excessive urination. Both *diabetes insipidus* and *diabetes mellitus* will produce large volumes of dilute urine, but only *diabetes mellitus* will produce urine with glucose in it.

Question 240

How would you treat *diabetes insipidus*? Does it matter whether it is caused by disruption to ADH secretion or AVPR2 function?

Answer 240

* Disruption to ADH secretion is easier to treat because the patient can be given desmopressin (= a synthetic version of ADH), which can be injected to maintain function. * Disruption AVPR2 function is much more difficult to manage because replacing a membrane receptor is very difficult. * This patient has enough ADH but lacks the necessary receptors for it to act on, so injecting desmopressin will not accomplish anything. * Gene therapy might solve this problem, but the technology is not sophisticated enough yet.

Question 241

Describe the role of RAAS in ion reabsorption and urine volume.

Answer 241

* Primarily through aldosterone * Reductions in blood volume trigger the RAAS, ultimately resulting in aldosterone secretion. * Aldosterone stimulates potassium secretion and sodium retention by stimulating the sodium/potassium ATP-ase pump. * Aldosterone in the DCT → enhances the rate of activity of the sodium/potassium pumps, amplifying the gradient for sodium reabsorption at the apical membrane * Aldosterone in the CD → aldosterone leads to the addition of EnaC channels (=sodium leak channels) and probably potassium channels to the apical surface, enhancing sodium reabsorption and potassium excretion. * Reducing potassium and reabsorbing sodium helps maintain ion gradients in the rest of the body and enhances the reabsorption/retention of water.

Question 242

Describe how aldosterone (and ADH) both contribute to the homeostasis of fluid in response to a loss of volume.

Answer 242

* **Sensors** → the JGA activates the RAAS, and angiotensin-II can stimulate ADH-secreting neurons (even if plasma osmolarity is normal) * **Effectors** → the cells of the DCT and CD increase both water and ion reabsorption.

Question 243

Give examples of important ion transporters and channels found in the DCT and CD. (not related to aldosterone and ADH)

Answer 243

* NCC (sodium chloride cotransporters) in the DCT contribute to overall sodium reabsorption * Calsium absorption involves several transporters, whose activity is regulated by PTH/calcitriol * Acid and nitrogenous compound secretion also involves specific proteins.

Question 244

How do disturbances of potassium in either direction *both* lead to arrythmias (or neural problems)?

Answer 244

* Muscle cells and neural cells are excitable (i.e., they can fire action potentials. * Potassium sets the resting membrane potential. * This would result in changes in repolarization in heart tissue. * The difference between resting membrane potential and threshold that is critical for whether neurons/muscle cells are constantly firing action potentials or never firing them. * If potassium equilibrium potential changes, the resting membrane potential changes and affects the ability to fire action potentials.