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CAPS390 > Final Exam > Flashcards

Final Exam Flashcards

1
Q

Ganglion

A

Cluster of nerve cell bodies in the PNS

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2
Q

Nucleus (Nerve)

A

cluster of nerve cell bodies in the CNS

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3
Q

Neurofilaments

A
  • structure of nerve cells esp. the dendrites and the axon
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4
Q

Microtubules

A
  • transport esp. vesicles of neurotransmitter
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5
Q

Smooth Endoplasmic Reticulum

A
  • extends from the soma to the axon terminal

- conveys the molecules/building blocks for membrane assembly

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6
Q

The 6 Steps of Synaptic Transmission

A
  1. Vesicle transport.
  2. Vesicle-loading.
  3. Depolarization.
  4. Exocytosis.
  5. Binding of NT.
  6. Depolarization.
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7
Q

Vesicle Transport of Synaptic Transmission

A
  • The vesicle is transported to the axon terminal via microtubules
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8
Q

Vesicle-loading of Synaptic Transmission

A
  • The Vesicle waits until there is a depolarization
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9
Q

Exocytosis of Synaptic Transmission

A
  • After there is a depolarization of the pre-synaptic cell the Loaded Vesicle then fuses to the plasma membrane with the help of SNARES and the neurotransmitters inside are releases into the Synapse
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10
Q

Binding of Neurotransmitters in Synaptic Transmission

A
  • the neurotransmitters bind to their corresponding receptor on the post-synaptic cell and cause a depolarization of the cell
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11
Q

Glia Cells

A
  • non-conducting cells that can enhance neurotransmission
  • provide biochemical (speed up impulses), structural, nutritive (growth and
    maintenance) , and immune (scavenge toxins, debris) support
  • there are 5 types of glia cells
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12
Q

Myelination of Axons

A
  • insulates the axon and prevents leaking of the ions
  • speeds up impulses
  • the thicker the myelin the faster the impulses go
  • amount of myelination correlates with the function of the nerve - conscious motor impulses need to move quickly so they are heavily myelinated
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13
Q

Schwann Cells

A
  • > myelinated axons
  • wrap around the axon of PNS cells to form many layers of plasma membrane called the myelin sheath
  • 1-2mm section of axon/cell
  • > unmyleinated axons
  • “swallow” 10 axons, but these axons can continue to communicate with the extracellular space in the PNS
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14
Q

oligodendrocytes

A
  • myelinate cells in the CNS (Same function as Schwann cells)
  • 60axons/cell
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15
Q

Protoplasmic and Fibrous Astrocytes

A
  • maintain local blood flow
  • scavenge ions and maintain homeostasis
  • acilitate/control transport across the ‘blood-brain barrier’ (BBB)
  • Protoplasmic astrocytes occur in grey matter
  • Fibrous astrocytes are found in white matter
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16
Q

Microglia

A
  • Immune scavengers; phagocytic/macrophage-like
  • continually extend and retract their processes
  • microglia to move their processes to the site of injury via chemo-atractants
  • in the CNS
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17
Q

Ependymal Cells

A
  • epithelium lining of: the surface of the brain beneath the pia mater, the inner surface of the brain ventricles, and the inner surface of the central canal of the spinal cord
  • Synthesize, secrete, and excrete cerebrospinal fluid (CSF)
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18
Q

Multiple Sclerosis

A
  • loss of central myelin.
  • Incidence rate is ~50/100,000 with
    death occurring within months to years (>20) of onset.
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19
Q

Amyotrophic Lateral Sclerosis

A

-loss of myelin, but this is secondary to the loss
of motor cells and skeletal muscle atrophy.
- The incidence rate is ~3-7/100,000, with death occurring within 2 - 6 years

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20
Q

Connective Tissue Coverings of the PNS

A
  • there are 4 connective tissue layers derived from mesoderm that cover both sensory and motor neurons
  • epineurium - outer layer
  • perineurium - middle layer
  • endoneurium - inner layer
  • Schwann cells
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21
Q

Connective Tissue Coverings of the CNS

A
  • there are 3 connective tissue layers derived from mesoderm
  • dura matter - outer layer
  • arachnoid mater - middle layer
  • pia mater - inner layer
  • there is a space between the arachnoid matter and pia matter called the subarachnoid space where small blood vessels travel that supply and drain both the brain and spinal cord.
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22
Q

Meningitis

A
  • caused by inflammation of the connective coverings of the brain and spinal cord (= meninges)
  • develops in response to infections, drug abuse, cancer, or physical injury
  • curable, but has devastating effects (e.g. dementia, death to the pressure on CNS structures) if left untreated
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23
Q

Blood Brain Barrier

A
  • formed by the epithelium that lines the blood vessels of the brain = capillary endothelium
  • Many tight junctions in endothelial cells prevent diffusion of macromolecules and ions across the endothelium
  • Not entirely impenetrable, as lipid-soluble substances can pass freely, and macromolecules and ions can be actively transported across this ‘continuous’ endothelium
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24
Q

Capillary Endothelium

A

formed by the epithelium that lines the blood vessels of the brain

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25
Q

Ventricular system

A
  • 4 cavities deep within the brain
  • Cerebral spinal fluid (CSF) fills the ventricules and helps to act as a liquid cushion to protect the
    brain against impact
    -
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26
Q

Cerebral Spinal Fluid

A
  • contains nutrients, neurotransmitters, and waste material
  • helps to protect the brain against impact
  • flows from the ventricles into the subarachnoid spaces where it is returned to the venous blood by small protrusions called ‘arachnoid villi’ that pierce through the dura mater
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27
Q

Choroid plexus

A
  • specialized clusters of ependymal cells that a simple cuboidal epithelium that
    surround collections or ‘tufts’ of capillaries within the ventricles.
  • actively transport water, ions, glucose and other solutes from the capillaries into the ventricles.
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28
Q

White matter

A
  • refers to collection of myelinated axons, and is involved principally in conduction of information from one location to another within the CNS and spinal cord via tracts
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29
Q

Grey Matter

A
  • refers to neuronal cell bodies
  • found in the cortices of the brain and the horns in the spinal cord. Grey matter principally integrates information at specific locations within the CNS
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30
Q

Blood

A

A specialized connective tissue that is composed of the formed elements (cells +
platelets) and the plasma (ECM)

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31
Q

Plasma

A
  • 90% water; 1% ions/gases; 9% protein

- Plasma without the clotting factors = serum

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32
Q

Formed Elements

A

blood cells and platelets

  • 3 main types
    1. Red Blood Cells (RBCs, erythrocytes)
    2. White Blood Cells ( = WBCs or leukocytes)
    3. Platelets
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33
Q

Red Blood Cells

A
  • Major cell type of blood
  • lifespan is 120 days; function completely inside the circulatory system
  • biconcave discs, ~8um diameter, and enucleate
  • well-developed cytoskeleton linked to transmembrane protein anchors that maintains shape and flexibility
  • Contain hemoglobin (Hb)
  • Contain ‘carbonic anhydrase’
  • Contain a few cystoplasmic organelles
  • Function in the circulatory system
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34
Q

Hemoglobin (Hb)

A
  • composed of a tetrapeptide plus a heme group

- Carry O2 and CO2

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35
Q

carbonic anhydrase

A
  • an enzyme that facilitates the generation of carbonic acid which breaks down into protons and bicarbonate ion. The latter is actively transported out of RBCs into the plasma where it acts as a major pH buffer
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36
Q

White Blood Cells ( = WBCs or leukocytes)

A
  • Travel within, but function outside, the circulatory system
  • adhere to and migrate through blood vessel walls to reach connective tissues in a process known as ‘diapedesis’
  • 2 types:
    1. Granulocytes - have granules
    2. Agranulocytes - don’t have granules
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37
Q

Granulocytes

A
  • prominent granules/secretory vesicles in cytoplasm
  • important in initiation ‘innate’ immune response (ie. inflammation)
  • 3 different types:
    1. Neutrophils
    2. Basophils
    3. Eosinophils
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38
Q

Neutrophils

A
  • Most abundant white blood cell (~60-70% of WBCs); very short-lived
  • Multilobed nucleus = polymorphonuclear (PMN)
  • Secretory vesicles do not stain well with Wright’s stain (therefore appear ‘neutral’) an
    contain anti-bacterial enzymes
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39
Q

Basophils

A
  • Represent less than 1% of WBCs, long-lived.
  • The granules contain histamine (vasodilator) and heparin (anticoagulant); together
    with mast cells responsible for boosting an inflammatory response
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40
Q

Eosinophils

A
  • Eosin stains basic proteins within the secretory vesicles/granules; short-lived
  • Compose 2% of the WBCs (white blood cells)
  • Active during later stages of innate and adaptive immune responses and are important for decreasing/ending the an immune response
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41
Q

Agranulocytes

A
  • cytoplasmic granules much less prevalent
  • there are 2 different types:
    1. Monocytes
    2. Lymphocytes
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42
Q

Monocytes

A
  • get activated to become macrophages in Connective Tissues
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43
Q

Lymphocytes

A
  • Important in highly specific ‘adaptive’ immune response
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44
Q

Platelets

A
  • Membrane-bound cell fragments released from ‘Megakaryocytes’ in bone marrow
  • Critical for ‘hemostasis’
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45
Q

hemostatis

A
  • platelet plug formation/clotting to stop bleeding into connective tissue spaces due to vascular damage
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46
Q

Thrombospondin and Platelet factor 3

A
  • important factors released that
    lead to further activation of platelets and the conversion of soluble plasma fibrinogen
    into insoluble fibrin fibers
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47
Q

Platelet Plug

A
  • Platelets, fibrin and trapped RBC’s form the plug
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48
Q

Platelet Activation

A
  • integrin-mediated binding to collagen in wounded blood vessels and the release of paracrine factors by blood vessel endothelial cells initiates release of granules inside via exocytosis.
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49
Q

chronic infection

A
  • increase in number of mature WBC is visible, while in Leukemia number of immature WBCs (ie. ‘Blasts’) increases in the peripheral blood
  • increased number of white blood cells in smear which is the same as leukaemia
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50
Q

chronic myelogenous leukemia

A
  • chromosomal translocation generates a constitutively activated form of the c-Abl cytoplasmic tyrosine kinase (a signal amplifier).
  • treatment: ‘Gleevac’ which is a c-Abl kinase inhibitor
  • greatly improved quality of life because the drugs are not grossly cytotoxic like most classical chemotherapeutics therefore the side effects are considerably reduced.
  • increased number of white blood cells in smear which is the same as a chronic infection
  • c-Abl kinase is constitutively activated (always turned ‘on’) (Activated by SCF)
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51
Q

Hemopoiesis = Hematopoiesis = Production of blood cells

A
  • Occurs in four different locations during embryonic, fetal and post-natal development (focus on myeloid stage)
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52
Q

Hematopoietic Stem Cell (HSC) = Hematocytoblast

A
  • can self-renew (generate more HSC)
  • Is pluripotent/multipotent as it can give rise, ultimately, to all of the cells of the blood and megakaryocytes that produce platelets.
  • Generates two distinct lineage progenitors
    1. Myeloid lineage progenitors
    2. Lymphoid Lineage progenitors
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53
Q

Myeloid lineage progenitors

A 
- differentiate to form (GEMM):
Granulocytes
Erythrocytes
Monocytes 
Megakaryocytes
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54
Q

Lymphoid Lineage progenitors

A
  • differentiate form B and T lymphocytes and Natural Killer Cells
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55
Q

Hematopoietic Cords

A
  • Regions in bone marrow that contains HSC, lineage progenitors, blasts, and supportive stromal cells where blood cell production takes place
  • located close to venous sinusoids (large, open capillaries), which allows cells to enter and leave bone marrow easily.
  • contain hematopoietic niches
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56
Q

Hematopoietic niches

A
  • made up of small clusters of developing blood cells and stromal cells within the larger Hematopoietic cords.
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57
Q

Regulation of Hematopoiesis

A
  • By growth factors, cytokines, colony stimulating factors produced by stromal cells in the bone marrow (ie. short range acting/paracrine factors). Ex. ‘Stem Cell Factor’ (SCF)
  • By hormones produced in another organ (long range acting) Ex. ‘Erythropoietin’ that acts on Erythroid lineage
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58
Q

Stem Cell Factor

A
  • Drives HSC and lineage progenitor cell proliferation
  • paracrine
  • SCF binds to c-Kit is a tyrosine-kinase linked transmembrane receptor on the HSC
  • which activates the intrinsic enzymatic activity of the receptor (tyrosine phosphorylation) which initiates multiple signaling pathways resulting in blast/precursor cell proliferation
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59
Q

Lineage restricted erythropoiesis = RBC synthesis

A
  • driven by the Erytroprotein hormone (EPO)
  • binds to to cell surface receptors on erythroid lineage cells that generate activated messengers (i.e. ‘STAT’s) that translocate to the nucleus and regulate transcription directly to push erythroblasts down the lineage to generate more RBC’s that are
    released into the circulatory system via the venous sinusoids
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60
Q

Erytroprotein hormone (EPO)

A
  • synthesized in the kidney in response to low O2 levels in the blood and travels to bone marrow in bloodstream
  • acts to increase the hematocrit in the blood. This increases oxygen carrying capacity of the blood.
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61
Q

2 Components of the Circulatory System

A
  • Lymphatic system

- Cardiovascular System

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62
Q

The Cardiovascular system consists of:

A
  • the heart (the pump)

- 2 circuits ( Pulmonary and Systemic)

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63
Q

The Blood Vessel Organization

A
  • Mesodermally derived
  • Central Lumen containing Blood
  • Innervated by autonomic nerves
  • outer wall consists of 3 layers (tunics)
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64
Q

Tunics

A
  • layers in the outer wall of blood vessels

- vary in tissue composition and structure depending on the vessel type and location

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65
Q

Tunica Intima (TI; Inner Layer)

A
  • simple squamous to cuboidal epithelium
  • basement membrane, and lamina propria (sub endothelial connective tissue)
  • Pericytes may be present, esp. in capillaries
  • internal Elastic Lamina is a thin layer of elastic C.T.
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66
Q

Tunica media (TM; Middle Layer)

A
  • the one that varies the most
  • variable amount and type of connective tissue (collagenous and elastic tissue)
  • Concentrically/circularly arranged smooth muscle cells (contractile portions of cells wrap themselves around the vessels horizontally)
  • concentrically/circularly arranged elastic fibres esp. abundant in big arteries
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67
Q

Tunica Adventitia (TA; Outer Layer)

A
  • may contain small blood vessels (Vasa Vasorum) that supply walls of large vessels
  • outermost connective tissue that varies in thickness and size
  • smooth muscle cells longitudinally arranged in large veins (contractile portions of cells extend up and down the vessel length-wise)
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68
Q

Arteries

A
  • transport blood AWAY from the heart to the lungs and tissues
  • Thicker tunics than veins b/c they are under higher pressure
  • three different types:
    1. Elastic Arteries
    2. Muscular Arteries
    3. Arterioles
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69
Q

Elastic Arteries

A
  • largest arteries
  • TI -> prominent collagenous lamina propria
  • TM -> thick and prominent with many elastic fibres = expansion and recoil during cardiac contraction/relaxation cycle
  • TA -> Vasa Vasorum (VV) to supple blood to wall of large vessel
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70
Q

Aortic Aneurysms

A
  • caused by the breakdown of elastin fibres due to age leading to ballooning of vessel walls
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71
Q

Muscular Arteries

A
  • Referred as “distributing” or “named” arteries
  • TI -> elastic fibres and fold when smooth muscle is contracted to decrease luminal diameter
  • TM -> prominent smooth muscle. Up to 40 layers of concentric smooth muscle cells
  • TA -> prominent collagenous connective tissue
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72
Q

Arterioles

A
  • smallest arteries
  • TI -> composed of endothelium, basement membrane, and little lamina propia
  • TM -> 1-3 layers of concentric smooth muscle
  • TA -> very little loose connective tissue (thin layer)
  • Innvervated by sympathetic (contraction/vasoconstriction) and parasympathetic (dilation) nerves
  • regulate blood pressure and flow into capillary beds via smooth muscle contraction, particularly at the “pre-capillary sphincters” of the very small “metarterioles”
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73
Q

Capillaries

A
  • smallest blood vessels in terms of diameter, thin walled
  • site of exchange of gases, nutrients, etc..
  • almost entirely TI
  • pericytes wrap around the endothelium
  • 3 types of capillaries: (differ in endothelium)
    1. Continuous Capillaries
    2. Fenestrated Capillaries
    3. Sinusoidal Capillaries = Venous Sinusoids
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74
Q

Continuous Capillaries

A
  • at highly-regulated exchange barriers b/t blood and the surrounding tissues
  • tight junctions b/t epithelial cells
  • exchange via vesicular transcytosis through the endothelial cells which can be tightly controlled for the amount of exchange and the specificity of the molecules exchange
  • Brain and lungs
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75
Q

Fenestrated Capillaries

A
  • at the sites of permissive exchange
  • exchange via small gaps = fenestrations in the epithelium that are not wide opem to to proteogylcans that fill the gaps and prevent the free movement of large plasma proteins in/out of the capillaries
  • in kidneys, intestine, and endocrine glands
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76
Q

Sinusoidal Capillaries = venous Sinusoids

A
  • at the site of free exchange
  • free echnage of maromolues and cells through large gaps in the endothelium
  • vessel diameter is larger than other capillaries
  • in bone, liver, and spleen
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77
Q

Veins

A
  • drain capillary beds, and return blood to the heart
  • low pressure/thinner tunics/increased lumen diameter
  • 3 different sizes/types:
    1. Venules
    2. Small and Medium Veins
    3. Large veins
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78
Q

Venules

A
  • post-capillary
  • larger diameter compared to arterioles
  • major sit of leukocytes diapadesis
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79
Q

Small and medium veins

A
  • fold to TI push into lumen to form valves that facilitate venous return to the heart and prevent the back flow of blood to the extremities
  • prominent TA, collagenous connective tissue
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80
Q

large viens

A
  • very prominent fibroelastic TA with some longitudinally arranged smooth muscle
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81
Q

Atherosclerosis

A
  • initial plaque formation is caused by subendothelial inflammation
  • swelling bulges into the lumen causing a narrowing = Stenosis
  • Stenosis causes blood turbulence and small injuries to the endothelial lining which leads to clotting within the lumen of the vessel (=thrombus)
    which can lead to fully blocking (=occluding) or pieces of the thrombus can break off and move further downstream in the arterial pathway (=embolus) where it can completely block smaller vessels
  • very damaging in small coronary arteries supplying the cardiac muscle (=mycarial infraction/heart attack) of the small vessels supplying critical brain regions (=ischemic attack/stroke)
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82
Q

Lymphoid System

A

lymphoid/immune system are responsible for defines against foreign invaders

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83
Q

Innate Immunity

A
  • rapid response
  • low specificity
  • Initiated by phagocytic activity of macrophages and neutrophils
  • Facilitated by natural killer cells that directly kill the target cells
  • involves complement proteins and toll like receptors (TLRs)
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84
Q

innate immune response

A
  • compliment proteins are released into connective tissue when there is a blood vessel injury or vasodilation
  • the proteins bind to lipids and carbohydrates on the pathogen’s surfaces with low specificity
  • the compliment proteins then bind to receptors on macrophages and neutrophils
  • Toll like receptors recognize various general pathogen molecules (LPS, and dsRNA)
  • the binding of a TRLs to a pathogenic molecule stimulates the macrophage/neutrophil to phagocytosis and destroy the pathogen
  • faciliated by natural killer cells (NK)
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85
Q

Compliment Proteins

A
  • produced by the liver
  • part of the innate response
  • bind to pathogen surface lipids and carbohydrates with low specificity
  • bind to receptors on macrophage/neutrophil
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86
Q

Toll-like Receptors (TLRs)

A
  • Surface of macrophages and neutrophils

- recognize general “pathogen” molecules such as LPS, dsRNA and specific glycoproteins

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87
Q

Natural Killer Cells

A
  • directly kill target cells
  • recognize viral infected and tumour target cells with low specificity
  • insert perforin into the target cell membrane
  • release interferon gamma
  • T-lymphocyte like cells
  • part of the innate immune response
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88
Q

Perforin

A
  • inserted in to the target pathogen cell by NK cells during the innate immune response
  • creates opens holes and the insides spew out killing the cell
  • innate immune response
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89
Q

Interferon gamma

A
  • innate immune response

- cytokine the recruits and helps macrophages/neutrophils

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90
Q

Inflammation

A
  • very strong innate immunity response
  • Granulocytes, agranulocytes, and dendritic/monocytic cells enter the connective tissue from the blood at the site of inflammation
  • which induces the release of cytokines (chemoattractants) by macrophages/neutrophils (interleukins) and NK cells (interferons)
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91
Q

diapadesis

A
  • the release of cytokines causes endothelial cells of post capillary venules to express cell adhesion molecules on their lumenal that bind to leukocytes
  • selectins initiate tethering and slow rolling of leukocytes on the endothelium
  • intergrins mediate firm adhesion and migration of leukocytes across the endothelium into the connective tissue
  • occurs during inflammation
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92
Q

Adaptive Immunity

A
  • acquired immunity; slower response
  • high specificity and memory
  • responds to specific antigens (molecular epitopes)
  • mediated by B and T lymphocytes
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93
Q

Primary Lymphoid Organs

A
  • lymphocyte production
  • naive, immunocompetent B cells produced in bone marrow
  • naive, immunocompetent T cells produced in bone marrow and thymus
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94
Q

B cell Development

A
  • in the bone marrow
  • proliferate and generate different clones of B-cells
  • differentiate into pre-Bcells
  • each pre B cell clone expresses a specific immunoglobulin (Ig) protein which recognizes a single antigen with high specificity
  • if the pre B cells binds a self-antigen it will be removed via apoptosis
  • remaining naive B cells are considered to be immunocompetent to respond to foreign antigens and leave the BM via venous sinusoids and travel to secondary lymphoid organ
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95
Q

T cell development

A
  • T lymphoblasts generated in the bone marrow migrate to the thymus via blood vascular system
  • differentiate into pre T cells
  • pre T cells express a specific T cell Receptor (TcR) which recognizes a single antigen at high specificity
  • if naive pre cells bind a self antigen it will be removed via apoptosis
  • remaining naive T cells are now immunocompetent to respond to foreign antigens and leave the thymus via blood vascular system to secondary lymphoid organs
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96
Q

Thymus

A
  • primary lymphoid organ
  • dense irregular connective tissue - meso derived
  • reticular epithelial cells form a network throughout thymus - endo derived
  • the trabecular/septa radiate inward from the outer capsule, dividing the thymus into lobules
  • each lobule is made up of:
    1. Cortex (outer layer)
    2. Medulla (inner layer)
  • contains epithelial reticular cells
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97
Q

Corticomedullary junction

A
  • entrance of developing T cells
  • exit of naive immunocompetent T cells
  • where clonal deletion occurs
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98
Q

Epithelial Reticular Cells

A
  • form the blood thymus barrier
  • present self-antigens to regulate clonal deletion at the corticomedullary junction
  • Hassall’s corpuscles are present in the medulla
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99
Q

Secondary lymphoid organs

A
  • sites of lymphocyte activation, upon encountering foreign antigens
  • there are 3 sites:
    1. Lymph Nodes (LN)
    2. Mucosa-Associated Lymphoid Tissue (MALT)
    3. Spleen
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100
Q

Lymph Nodes

A
  • secondary lymphoid organ
  • dense irregular CT capsule and true reticular/netlike CT (collagen III) stroma
  • path of the lymph flow
  • enters via afferent lymph vessels, percolates over lymphocytes in cortex and paracortex and leaves via efferent lymph vessels
  • B cells get activated in the cortical nodules
  • T cells get activated in the paracortex
  • activated T cells and B cells enter and exit via the post-capillary venules
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101
Q

Mucosa-Assocaited Lymphoid tissue (MALT)

A
  • secondary lymphoid organ
  • sub epithelial aggregates of lymphoid tissue
  • site of B and T cell activation
  • No capsule or afferent lymphatics -> no lymphatic flow through it
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102
Q

Spleen

A
  • secondary lymphoid organ
  • connective capsule (outside) and venous sinusoids for easy migration of RBC’s and WBC’s in and out of the circulatory system
  • contains white pulp and red pulp
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103
Q

White Pulp of the Spleen

A
  • site of B and T cell activation
  • germinal centres house B cells
  • peri-arteial lymphatic sheaths (PALS) house T cells
  • where dendritic cells from the marginal zone present antigens to the T cells
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104
Q

Red Pulp of the Spleen

A
  • site of old red blood cells destruction by macrophages located in the “marginal zone”
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105
Q

Lymph Vascular System

A
  • moves lymph fluid absorbed from the connective tissues back to the venous system
  • blind-ended start lymphatic capillaries have very few tight junctions between endothelial cells
  • capillaries coalesce into larger lymphatic vessels, have very scanty tunics, all drain back to major subclavian veins in neck and empty lymph fluid into them
  • one way flow (one way valves)
  • normally no RBC’s in lymph vessels
  • often run along blood vessels
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106
Q

Skin - general info

A
  • largest organ in the body
  • protective and waterproof layer
  • regulates body temp via sweat
  • contains sensory neverves to detect temperature, pain, pressure, and touch
  • there are 2 layers:
    1. epidermis
    2. dermis
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107
Q

Epidermis

A
  • outer layer of stratified squamous keratinized epithelium made up of keratinocytes - derived from ectoderm
  • forms specialized skin appendages such as sweat, sebaceous glands and hair follicles
  • specialized cell types - Melanocytes, Merkel cells, Langerhan cells
  • no vasculature
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108
Q

Dermis

A
  • underlying layer of dense irregular CT derived from mesoderm
  • attached to epidermis by hemidesmosomes
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109
Q

Five layers of Epidermis

A

(basal to apical)

  1. Stratum Basale
  2. Stratum Spinosum
  3. Stratum Granulosum
  4. Stratum Lucidum
  5. Stratum Corneum
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110
Q

Stratum Basale

A
  • undifferentiated highly mitotic stem cells
  • cuboidal to low columnar epithelial cells/keratinocytes
  • desmosomes at cell-cell interfaces and hemidesmosomes at cell-basement membrane
  • contains the stem cells for skin and the cells move apically and differentiate
  • contains melanocytes and Merkel Cells
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111
Q

Melanocytes

A
  • produce skin pigment
  • neural-crest derived
  • migrate into the epidermis and reside in the stratum basale
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112
Q

Merkel Cells

A
  • mechano/touch receptors
  • neural-crest derived
  • migrate into the epidermis and reside in the stratum basale
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113
Q

Stratum Spinosum

A
  • differentiation of the epithelial keratinocytes begins as the cells begin to produce large numbers of keratin intermediate filaments (= tonofilaments)
  • desmosomes are very prominent at all cell-cell interaction points at the ends of small keratinocyte cell processes
  • contains Langerhans cells
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114
Q

Langerhans Cells

A
  • hematopoietic stem cell-derived antigen-presenting cells (APC’s = dendritic cells)
  • they migrate into the epidermis and primarily reside in the stratum spinosum
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115
Q

Stratum Granulosum

A
  • cells begin to fully differentiate and flatten/become squamous
  • generate lipid-rich vesicles/granules
  • lipid is exocytosed to generate a waterproof barrier between s. granulosum and s. lucidum
  • produce proteinacious ‘keratohyalin’ that forms cytoplasmic ‘granules’ (not membrane- bound/vesicular) cross-links the keratin tonofilaments
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116
Q

Stratum Lucidum

A
  • above the waterproof barrier these cells fully differentiate by producing ‘eleidin’ a protein that aligns the cross-linked keratin tonofilaments in parallel arrays
  • as these cells are above the waterproof barrier they start to die and lose their nuclei
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117
Q

Stratum Corneum

A
  • Enucleate flat cells that are completely dead
  • filled with protective cross-linked and bundled keratin filaments = ‘squames’
  • as desmosomes deteriorate the loss of junctions allows squames to slough off (desquamated)
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118
Q

Hair follicles

A
  • Formed from invagination of the epidermis that push down into the dermis
  • Terminate at the ‘hair root’ (epidermal) where dermal papilla indents to supply blood vessels and nerves to the area of the hair root
    Contains:
  • The outer external root sheath of the hair follicle
  • The inner internal root sheath of the hair follicle
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119
Q

Outer external Root Sheath of the hair follicle

A

modified stratum basale and stratum spinosum

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120
Q

Inner internal root sheath of the hair follicle

A

differentiating stratum granulosum- like cells that produce very ordered/regularly arranged cells that move inward and die to produce to the hair shaft (analagous to the s. lucidum and s. corneum but organized into layers = cuticle, cortex and medulla moving from outside in)

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121
Q

Sebaceous Glands

A
  • form as an out pouching of the hair follicle epidermis above hair bulb
  • ducts may branch slightly and empty into hair canal (the small space between the fully formed hair shaft and follicular epithelium)
  • alveolar secretory portion secretes lipid-rich sebum that stains palely by H&E
  • mode of secretion is by necrosis/death of the secretory cells – all contents released
    (holocrine secretion)
  • obstruction of ducts leads to bacterial infection which contributes to acne formation
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122
Q

Eccrine/ Regular sweat glands

A
  • Simple, coiled tubular glands that form as invaginations of the epidermis that is widely distributed throughout the skin
  • secrete watery ‘sweat’ with a slight mucous content by regular, polarized, exocytosis-based secretion (merocrine secretion)
  • secretory portion of tubules have contractile cells embedded in them which are epithelial and ectodermally derived that help expel secretory products into ducts efficiently (= ‘myoepithelial’ cells that are also very prominent in mammary glands of the breast
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123
Q

General Organization of Internal Tubes

A
  1. Mucosa (inner layer)
  2. Submucosa (middle layer)
  3. Adventitia (outer layer)
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124
Q

Mucosa

A
  1. Epithelium (lining the lumen) - endodermally derived

2. lamina Propria - loose CT with MALT

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125
Q

Submuscosa

A

various CT types

may contain exocrine glands

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126
Q

Adventitia

A

CT may contain muscle, cartilage, or bone depending on the location and function of the tube

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127
Q

Respiratory System Functions

A
  • conducts air in/out of the lungs

- exchange of oxygen and carbon dioxide in the lungs

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128
Q

Trachea

A

-Major conducting airway in neck and thorax
-Single tube, not paired
-Seromucociliary clearance; lumen is always open, but diameter regulated regulated slightly via
smooth muscle (decreases diameter when contracted) and elastic CT (facilitates reopening when smooth muscly is relaxed)

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129
Q

Muscosa layer of the Trachea

A
  • Respiratory epithelium (ciliated, pseudostratified epithelium with goblet cells):
    a. Columnar Cells with apical motile cilia for seromucociliary clearance; beat upwards toward pharynx
    b. Goblet Cells: unicellular exocrine glands; secrete mucous apically; have a few apical microvilli
    c. Small Mucous Granule cells (smg) : secrete paracrine factors basally; some secretions regulate smooth muscle contraction (and, thus, lumen diameter)
    d. basal (stem) cells
  • Lamina propria : loose CT + MALT; Elastic lamina (for recoil) at interface of mucosa and submucosa
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130
Q

Submuscoa layer of the Trachea

A

-Dense fibroelastic CT; Seromucous glands: exocrine; complex acinar

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131
Q

Adventitia layer of the Trachea

A

-Contains hyaline cartilage rings (C-shaped) with smooth muscle that connects the ends of “C” posteriorly.

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132
Q

Pharynx

A

-Common air and food passage, funnel-shaped withmuscular (ie. not cartilaginous) walls

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133
Q

Epithelium of the Pharynx

A

mostly lined by some respiratory epithelium and considerable stratified squamous
epithelium due to friction of food bolus passing through

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134
Q

Lamina Propria of the Pharynx

A

contains large M.A.L.T aggregates (eg. pharyngeal ‘tonsils’)

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135
Q

Submuscosa of the Pharynx

A

contains seromucous glands whose ducts empty onto lumenal surface

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136
Q

Adventitia of the Pharynx

A

contains skeletal muscle (eg. for swallowing = conscious/voluntary)

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137
Q

Larynx

A
  • Small box between pharynx and trachea

- consisting of the Roof and the Floor

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138
Q

Roof of the larynx

A

Epiglottis; functions to keep food and fluid from entering the larynx and trachea;
therefore closed during swallowing; open during breathing

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139
Q

Floor of the Larynx

A

bilateral folds of mucosa and submucosa that push into the lumen = ‘vocal
fold

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140
Q

Epithelium of the Larynx

A

lined by pseudostratified ciliated columnar epithelium EXCEPT on the surfaces of epiglottis and vocal folds. These are often covered by stratified squamous epithelia due to the increased friction because of movements of the epithelia against one another in these areas during either swallowing or vocalizing; sometimes keratinized, especially over the vocal folds.

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141
Q

Lamina Propria of the Larynx

A

loose CT with some elastic fibers

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142
Q

Submucosa of the Larynx

A

CT with some seromucous glands; additionally, the free edge of each vocal fold is
reinforced by very dense CT = ‘vocal ligament’

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143
Q

Adventitia of the Larynx

A

Elastic cartilage in epiglottis (for flexibility); the skeletal muscle fibers of the ‘vocalis
muscle’ attach to the sub-mucosal vocal ligaments and when they contract they increase the tension/taughtness of the vocal cords such that they vibrate and produce sound waves when air passes over them.

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144
Q

Nasal Cavity

A
  • Mucociliary clearance, cilia beat back towards pharynx; highly vascularized lamina propria; little submucosa; bone and/or cartilage very prominent in the adventitia
  • Continuous with paranasal sinuses = restricted spaces that cannot expand, especially the passageways between the two which can become plugged due to inflammation in the lamina propria (can lead to ‘sinusitis’)
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145
Q

Epithelium of the Nasal Cavity

A

Respiratory, except for anterior-most portion near nostrils where it merges with stratified squamous epithelium of the skin outside the nostrils

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146
Q

Lamina Propria of the Nasal Cavity

A

Loose CT; large venous sinuses/highly vascularized to warm nasal cavity and the paranasal sinuses as air passes through; mucous glands are present.
** Mucociliary clearance due to goblet cells in respiratory epithelium, and simple mucosal glands
in lamina propria (ie. very little ‘serous’ component in most of the nasal cavity = thicker
secretions than trachea and bronchi below).

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147
Q

Submucosa of the Nasal Cavity

A

almost non-existent

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148
Q

Adventitia of the Nasal Cavity

A

contains hyaline cartilage anteriorly, and bone posteriorly

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149
Q

Olfactory Mucosa

A

specialized mucosa in roof of the nasal cavity

150
Q

Olfactory Epithelium

A
  • modified respiratory epithelium
    -Contains Olfactory Cells (=sensory neurons). Dendrites end in modified sensory cilia which
    are embedded in odorant-containing serous secretions
    -Also contains basal stem cells and supportive columnar ‘sustentacular cells’
151
Q

Olfactory Lamina Propria

A

contains Bowman’s serous glands whose ducts open on free epithelial surface; watery secretions trap ‘odorant’ chemicals on the such that receptors on sensory dendrites of olfactory cells are activated by them to initiate modified action potentials which are perceived as senses of smell.

152
Q

Bronchi

A
  • Begin at the bifurcation of the trachea and branch ~8 times in each lung. -Diameter decreases with each branching
  • Branches of pulmonary artery (low O2 ) and veins (high O2 ) run in adventitia
153
Q

Bronchi Trends as the diameter decreases

A

o Decrease in amount of cartilage in the adventitia(arranged as plates, not rings)
o Decrease in number of submucosal seromucous glands and goblet cells
o Decrease in height of epithelial cells
o Increase in smooth muscle and elastic tissue in the mucosa and submucoa

154
Q

Cystic Fibrosis

A
  • Poorly trafficked CFTR mutants leads to disrupted Cl- secretion/H2O balance which leads to a thickening of mucous secretions that are deposited over the respiratory epithelium and within ducts of submucosal glands. Consequently, cilia cannot beat efficiently to clear debris
  • Over time, microorganisms are trapped in the mucous and recruit many innate immune cells; eventually chonic inflammation occurs in the lamina propria which leads to…
  • Fibrosis = accumulation of collagen I fibers and loss of elastic fibers that impedes airflow deeper into the bronchioles and alveoli
155
Q

Bronchioles

A

-Continuous with bronchi
-Branch approximately 6 more times to reach terminal bronchioles (end of conductive portion of respiratory tract)
-Histology is significantly different from trachea/bronchi:
o Simple columnar/cuboidal epithelium; ciliated cells and Clara cells (secrete lubricating lipoprotein synthesis; helps keep airways open/patent)
o Very few to know goblet cells loss of seromucous submucosal glands o No adventitial cartilage

156
Q

Respiratory Portion of the Respiratory System

A
  1. Respiratory Bronchioles

2. Alveoli Proper

157
Q

Respiratory Bronchioles

A

Discontinuous bronchiolar tissue that is interrupted by alveolar air sacs (tiny grape-like out-pouchings). There is some gas exchange here, but the majority occurs in the alveoli proper.

158
Q

Alveoli Proper

A

-Site of gas exchange with adjacent alveolar capillaries
-Composed of a simple epithelium with a thin lamina propria between
adjacent alveoli = interalveolar septum =reticular connective tissue with elastic fibers.

159
Q

Alveolar Epithelial Cell Types:

A
  • simple squamous pneumocytes (type I)

- cuboidal pneumocytes (Type II)

160
Q

Simple squamous pneumocytes (Type I)

A
  • simple squamous epithelium with tight junctions between cells.
  • derived from the terminal portion of pulmonary arterioles (with the intervening basal laminae from the two epithelia).
  • the site of gas exchange.
161
Q

Cuboidal pneumocytes (Type II)

A

interspersed among the type I pneumocytes. They produce and secrete surfactant which is a lubricating phospholipoprotein secretion that reduces surface tension to keep the alveoli open/patent. Lamellar bodies are secretory vesicles within these cells that contain surfactant (these are very characteristic of these cells in TEM’s.

162
Q

Alveolar Dust Cells

A

Alveolar macrophages that phagocytose particulate matter within the
alveoli (e.g. particles from cigarette smoke). Chronic activation of dust cells lead to longterm inflammatory responses that can cause the cumulative breakdown of the reticular/elastic connective tissue of the lamina propria, effectively destroying the interalveolar septa which leads to a loss of functional alveoli.

163
Q

Emphysema

A

Chronic inflammation leads to scarring/fibrosis of intralveolar septa which lose elasticity and reticular fibers; as a result alveolar tissue is eventually lost as are associated alveoli; rarely regenerates completely.

164
Q

Digestive System Consists of:

A
  1. Oral Cavity
  2. Alimentary Canal = GI tract
  3. Accessory Glands
165
Q

Oral Cavity functions

A

-Functions in ingestion, taste, mastication (chew), formation of bolus (ball of chewed food) formation, and deglutition (swallowing) by moving bolus to pharynx posteriorly

166
Q

The 3 parts to the lips:

A
  1. External Aspect
  2. Intermediate/Vermillion zone
  3. Internal Aspect
167
Q

The External Aspect of the lip

A
  • Is continuous with skin and has the same histology

- Stratified squamous keratinizing epithelium

168
Q

The Intermediate/ Vermillion Zone of the lip

A

-Pinkness/redness is due to highly vascularized lamina propria -No hair or sweat and/or sebaceous glands

169
Q

The Internal Aspect of the lip

A

-Continuous with the cheeks (=Wet Mucosa)/ similar histology to the
cheeks
-Epithelium: non-keratinized stratified squamous
-Lamina propria: dense irregular C.T.
-Submucosa: contains mucous glands to keep lips moistened
-Adventitia: skeletal muscle (the orbicularis oris muscle, which is responsible for the puchering/movement of lips)

170
Q

Gingiva=Gums

A

-The junctional epithelial collar is a thickening of epithelium around the tooth
- acts as a bacterial barrier to protect the periodontal ligament
-Epithelium: lightly keratinized stratified squamous epithelium
-Lamina propria = dense irregular CT, has prominent Collagen I fibers that mingle
with the periodontal ligament that anchors the root of the tooth in place. -Adventitia = bone (upper maxilla and lower mandible jaws)

171
Q

Teeth are composed of:

A
  1. Enamel
  2. Dentin
  3. Pulp
172
Q

Enamel

A
  • highly mineralized, but has no regenerative ability
  • not innervated (produced by Ameloblasts that are derived from oral ectorderm/dental placode; lost after tooth erupts).
  • 96% hydroxyapatite/mineralized (very hard).
173
Q

Dentin

A 
highly mineralized (although less so than enamel), 70% hydroxyapatite/mineralized, has regenerative ability, and is innervated (produced by Odontoblasts derived from mesenchyme retained after tooth
erupts)
174
Q

Pulp

A
  • loose CT with high GAG content
  • vascularized and innervated
  • sits in the pulp cavity deep in the root of the tooth
  • blood vessels and nerves enter/exit the pulp cavity via the root canal
175
Q

Odontogenesis (tooth formation)

A
  • begins in ~6 weeks after gestation
  • 3 steps:
    1. Induction
    2. Morphogenesis
    3. Development
176
Q

the induction of Odontogenesis

A
  • Dental placode (oral ectroderm) forms above mesenchyme
  • paracrine signaling back and forth between dental placode and mesenchyme (SHH/BMPs) induces differentiation and dental placode that then sinks into the mesenchyme
177
Q

Morphogenesis of Odontogenesis

A
  • After placode sinks, it forms a folded cap (enamel organ that gives rise to ameloblasts that secrete/deposit extracellular enamel).
  • Mesenchyme underneath condenses to form a layer of odontoblasts (secrete/deposit extracellular dentin).
  • Pulp, which forms directly from mesenchym lays beneath the ameloblasts
  • Lateral to the enamel organ, mesenchyme differentiates to form the the periodontal ligament and the cementum
178
Q

Development of Odontogenesis

A

Ameloblasts die after tooth erupts to reveal enamel it produced underneath (thus, no regenerative potential in the enamel)

179
Q

Crown

A

has 2 parts:

  1. Anatomical Crown
  2. Clinical Crown
180
Q

Anatomical Crown

A
  • portion of tooth entirely covered by enamel
  • surrounded by a collar of ‘Junctional Epithelium’ from the gingiva that protects against invasion of pathogens (if protection breaks down chronic inflammation occurs in the underlying lamina propria of the gingiva = gingivitis (when extreme and long lasting can affect the periodontal ligament also such that the teeth become ‘loose’)
181
Q

Clinical Crown

A
  • enamel above the gingiva (eg. visible portion of tooth)
182
Q

Periodontal Ligament

A
  • Dense regular connective tissue (from mesenchyme/mesoderm)
  • Suspends/holds the tooth in place
  • Attaches to surrounding bone and the cementum; its fibers (collagen type I) radiate into the lamina propria of the gingiva above the bone
  • It’s highly regenerative, vascularized, and innervated
183
Q

Cementum

A

-Directly attached to the outer aspect of the dentin along the root of the tooth
-Is bone-like and it is produced by ‘cementoblasts’ (similar to osteoblasts)
-Resorbed and re-modeled by by ‘odontoclasts’. (similar to osteoclasts)
-This layer allows for orthodontic apparatus (e.g. braces) teeth within the
alveolar sockets.

184
Q

Alveolus

A

-Socket of spongy bone in Mandible/Maxilla (eg. upper and lower jaw bones)

185
Q

Palate = Roof of Oral Cavity

A
  • Separates the nasal and oral cavities
  • 2 parts:
    1. Hard palate
    2. Soft Palate
  • Hard palate is located anteriorly, and soft palate is posterior (towards pharynx)
186
Q

Hard Palate

A
  • Epithelium is stratified squamous, keratinized for protection while chewing
  • Adventitia contains bone
187
Q

Soft Palate

A

-Epithelium is stratified squamous, non-keratinized
-Adventitia contains skeletal muscle; contracts to elevate soft palate during
swallowing to prevent food going upward into nasal cavity
-Elevates with uvula during swallowing to close nasal cavity entrance to
pharynx

188
Q

Tongue = Floor of the Oral Cavity

A
  • Papillae = mucosal posts/specializations
  • A single papilla consists of a covering stratified squamous, keratinized epithelium, and a core of lamina propria, which contains dense irregular C.T.
  • lamina propria: contains lymphoid aggregates/M.A.L.T. = lingual tonsils
  • submucosa: Serous glands, the secretions trap “tastant” molecules such that receptors on the dendritic microvilli of sensory receptors of taste buds can bind them (similar to what occurs in the olfacotry epithelium
  • Adventitia contains skeletal muscles (intrinsic tongue muscles)
189
Q

Taste Buds

A
  • The taste buds are located within the epithelium and they look pale in H&E-stained light microscopic images.
  • Consist of clusters of spindle- shaped sensory receptor cells: each of these cells has a long, slender dendritic microvilli that protrude from the apically-located taste pore
  • ‘Tastants’ chemicals interact with G-protein-coupled receptors and ion-channels on microvilli which causes the sensory receptor cells to depolarize
  • leads to a synapse-based activation of sensory nerves basally and transmit via cranial nerves
190
Q

Esophagus

A
  • Muscular tube that does no active digestion or absorption

- A conduit for transporting food from the pharynx to the stomach

191
Q

Mucosa of the Esophagus

A
  • stratified squamous, usually non-keratinized, protective

- Lamina Propria = Loose connective tissue

192
Q

Submucosa of the Esophagus

A
  • Dense irregular C.T that contains seromucous glands (anti-bacterial serous secretions, and lubricating mucous secretions)
193
Q

Muscularis Externa of the Esophagus

A

o Upper portion is skeletal muscle/voluntary (important for swallowing); continuous with sk. muscle of pharynx above it
o Lower portion is smooth muscle/involuntary (important for rhythmic, peristaltic contractions)
- ends at lower esophageal/cardiac sphincter

194
Q

Stomach =Gastric:

A

-Initiates digestion (breakdown of food products)

195
Q

Mucosa of the Stomach

A

o Simple columnar epithelium with depressions = gastric glands
o Apically directed luminal epithelial secretions = mucous, acid, and digestive enzymes (zymogens)
o Basal epithelial secretions = hormones and paracrine factors
o Rugae: transient gastric mucosal folds. The folds are flatten when the stomach is full
- Stomach Cells

196
Q

Muscularis Externa of the Stomach

A
  • smooth muscle: thickenings at esophageal/cardiac and also duodenal/pyloric openings (= sphincters that control flow of lumen contents from one portion of the GI tract to another)
197
Q

Gastro-Esophageal Junction (esophagus to stomach)

A
  • abrupt transition from stratified squamous to columnar epithelium
  • Seperated by Lower esophageal/Cardiac Sphincter
198
Q

Barrett’s Esophagus

A
  • most often caused by acid reflux (heart burn) from stomach back into the esophagus, which induces ‘metaplasia’ of the esophageal mucosa such that it comes to resemble that of the stomach; when long term and chronic, this can lead to pre-malignant lesions
199
Q
  • Gastro-Duodenal Junction (stomach to small intestine)
A
  • Site of prominent thickening of sm. muscle in the muscularis externa = pyloric sphincter
  • Gastrin causes relaxation of sphincter; release of chyme into the duodenum
200
Q

Small Intestine

A
  • Final digestion of food by pancreatic enzymes that are released into the lumen of the duodenum
201
Q

Absorptive Mucosa of the Small Intestine

A

o Mucosal protrusions = villi (epithelial covering with a core of
lamina propria/loose connective tissue)
o Mucosal depressions = crypts/glands

202
Q

Epithelium of the Small Intestine

A

o Simple columnar epithelium, polarized with tight junctions
o Absorptive “Enterocytes” with apical microvilli to increase surface area for absorption (mediated by transmembrane ion channels and molecular transporters) with a mucinous coating (= glycocalyx that traps activated zymogens for terminal digestion of proteins, carbohydrates and lipids that are then absorbed)
o Goblet cells: apically-directed secretion of protective mucous
o Paneth cells: eosinophilic secretory vesicles - released apically contains anti-bacterial lysosyme; can also become antigen presenting cells; found deep within the crypts/glands at their base

203
Q

Lamina Propria of the Small Intestine

A

o Loose C.T, contains many vascular and blind-ended lymphatic capillaries (“central lacteals” in core of villi)
o Prominent M.A.L.T which contains B and T lymphocytes aggregations that are activated by specific antigens from pathogens that are found in the GI tract.

204
Q

Submucosa of the Small intestine

A

o Contains Brunner’s Glands which are exocrine glands that secrete alkaline mucous to both protect and neutralize acid entering the small intestine from the stomach

205
Q

Large Intestine

A
  • Colon to Rectum
    o Highly absorptive, mostly for water and ions
    o Mucosa - absorptive; enterocytes and many goblet cells; crypts/glands present, no villi present
    o Submucosa - dense irregular connective tissue, no Brunner’s glands
206
Q

Hemorrhoidal Veins

A

the mucosa and submucosal connective tissues at the junction of the rectum and the anus contains numerous large diameter, thin-walled hemorrhoidal veins

207
Q

Digestive Glands

A
  • Develop from evaginations of endodermal tube near the start of intestine where all three glands drain into the small intestine (Pancreas, Liver, and Gall bladder)
208
Q

Development of GI Glands

A
  • Beginning as an endodermal tube, gall bladder branches out as an out pouching
  • Further from the out pouching, the liver develops and forms and is joined by the common hepatic duct
  • Ventral part of pancreas develops with the out pouching, and joins with dorsal part of pancreas which develops opposite to the out pouching
  • All ducts empties at Sphincter of Oddi into the small intestine.
209
Q

Pancreas

A
  • exocrine gland that secretes digestive enzymes apically into a duct
  • endocrine gland that secretes hormones basally into the connective tissue where they are picked up by fenestrated capillaries for distribution throughout the body.
  • Secretory activity of exocrine pancreatic cells stimulated by the hormone cholecystokinin (CCK) produced by DNES cells
  • Secretions have a serous component which is disrupted by mutations in the CFTR.
210
Q

Endocrine Islets:

A
  • made up of clusters/islets of endocrine cells without ducts.
  • Pale/chromophobic cells with H & E staining (L.M.)
  • Small secretory vesicles (E.M.)
  • Two major cell types, discerned by immunostaining specific for peptide hormones/secretory
    product:
    -> α cells = secrete glucagon which increases the blood glucose
    -> β cells = secrete insulin which decreases the blood glucose.
211
Q

Exocrine Acini

A
  • release their secretions apically into ducts.
  • there are 2 types of cells:
    1. Acinar cells=zymogenic cells
    2. Centroacinar cells
212
Q

Liver

A
  • It is located in the upper right-hand quadrant of the abdominal cavity, just inferior to the diaphragm and it has numerous functions that are all carried out in the same cells (hepatocytes).
  • Functions are:
    1. Exocrine (eg. bile production/secretion)
    2. Endocrine (eg. plasma protein/lipoprotein production/secretion)
    3. Detoxification (via transmembrane enzymes in the SER)
    4. Storage of glycogen (polymerized form of glucose = electron dense granules in
    hepatocyte cytoplasm, regulated by insulin and glucagon)
  • Bile exits the liver by the hepatic bile duct
  • it has a dual blood supply into it
213
Q

Hepatic “Portal Triad”

A
  • Branches of the hepatic artery, hepatic portal vein, and the hepatic bile duct travel together as the Portal Triad
214
Q

Hepatocytes:

A
  • Highly synthetic (large amounts of RER, SER, euchromatin) and highly metabolic (large numbers of mitochondria) with a very high storage capacity (eg. many glycogen granules)
  • In order to have the same cells function in both endocrine and exocrine signaling, the cells have
    specific secretory domains (this is a type of cell polarity)
215
Q

Cirrhosis of Liver

A
  • Degenerative liver disease characterized by an increase scarring/ fibrosis which increases the connective tissue greatly
  • often due to chronic inflammation, as well as a degeneration of the hepatocytes and blockage/loss of venous sinusoids
  • leads to hypertension (increased pressure) in the hepatic portal vein as blood from the GI tract cannot move through the liver.
216
Q

Gall Bladder

A

• Small, pear-shaped organ situated on the inferior aspect of the liver that concentrates and stores the bile and releases it into the duodenum as required.

  • Mucosa: Absorptive simple columnar epithelium, very few goblet cells; overall the mucosa is highly folded without clearly organized villi or crypts/glands
  • Muscularis has no defined muscularis mucosa; however, there is a very thick ‘muscularis’ of overlapping layers of smooth muscle that is analgous to the muscularis externa in the GI tract.
217
Q

Urinary System

A
  • Produce and excrete urine/removal of toxic by-products (urea) from metabolic activity -Actually a modified exocrine system
  • Regulates plasma volume and blood pressure
218
Q

Kidneys

A
  • Are large, reddish, bean-shaped organs located on the posterior abdominal wall
  • encapsulated by a dense irregular C.T. capsule
  • Mesodermally-derived and highly vascularized
  • Blood vessels and ureters enter and exit the kidney at the ‘hilum’
219
Q

Renal Corpuscle (in the cortex)

A
  • Produces glomerular filtrate (pressure-based)
  • Contains:
  • > the Bowman’s Capsule
  • > Glomerular capillaries (in capsule)
  • > Urinary space (contains glomerular filtrate)
  • > Vascular Pole
  • > Glomerular Filtration Barrier
220
Q

Proximal Tubule (Cortex to Medulla)

A

-Site of reabsorption of most of the ions, glucose, amino acids, and water from the filtrate into the peritubular loose connective tissue (and ultimately back into the blood via the peritubular capillaries)
-Simple cuboidal epithelium with very high number of microvilli and many mitochondria due to the high demand of active transport (lots of Na pumps)
-Highly absorptive:
o ~75% NaCl /H2O resorption via pumps and channels
o ~90% glucose resoption via pinocytosis/endocytosis

221
Q

Loop of Henle (Medulla)

A

-Simple squamous epithelium
-Consists of two parts:
1. Descending limb:
B. Ascending limb:

222
Q

Distal Tubule: (Medulla to Cortex)

A
  • Simple cuboidal epithelium
  • Pumps NaCl into peritubular CT of medulla
  • Water impermeable
  • Contains high H20/low salt ‘dilute’ urine
  • Helps modify urine via the Macula Densa, which is part of the Juxtaglomerular apparatus
    (JGA)
    -Macula densa: simple columnar cluster of cells that contact the juxtaglomerular
    cells at the vascular pole of the renal corpuscle
    -> contains sensors detects high volume and low salt/dilute urine (= the ‘diuretic’ state)
    -> stimulates juxtaglomerular cells via gap junctional communication
223
Q

Juxtaglomerular apparatus: (adjacent to the capillary of glomerulus at the vascular pole of the corpuscle)

A
  • Macula Densa: columnar epithelium that are the result of the thickening of the distal tubule
  • High volume urine (diuretic state) stimulates cells which leads to gap junction mediated signaling to juxtaglomerular cells
  • Junxtaglomerular cells are modified pericytes of glormerular arterioles that secrete renin upon stimulation by the Macula Densa
224
Q

Collecting Tubules: (span from cortex to medulla)

A
  • not part of nephron.
  • join with the continuous ‘Uriniferous Tubule’ (=Nephron +Collecting Tubule).
    -Simple cuboidal to low columnar epithelium
    -Normally are water impermeable which results in high volume of dilute urine
    (=Diuretic state)
    -Drain to renal ‘Renal Pelvis’, which ultimately funnels to the ureter
225
Q

Excretory Passages of Urinary System

A

-All have a distensible mucosa and a muscularis externa that is functionally different in each structure

226
Q

Ureters

A
  • Mucosa: distensible with transitional epithelium and a fibroelastic lamina propria
  • Muscularis externa: smooth muscle in two layers, inner longitudinal/outer circular layer (ie. the opposite orientation to that found in the GI tract) that undergoes rhythmic peristaltic contractions to move urine down the ureter towards the bladder.
227
Q

Bladder

A

-Mucosa: similar to ureter with a thicker fibroelastic lamina propria and little submucosa.
-Muscularis externa: interlaced smooth muscle for expulsion into urethra upon contraction
- Contains an external sphincter and an internal sphincter
- Composed of transitional epithelium

228
Q

Transitional Epithelium (Urothelium)

A
  • Stratified, but cells change shape as lumen fills and epithelium ‘distends’ (go from cuboidal to squamous)
  • Lots of demosomal cell-cell adhesions and also contain pleated portions which helps provide surface extra for the bladder expand
  • As cells flatten desomosomal cell-cell adhesions are maintained but there is an unfolding of membrane between adhesions
229
Q

Urethra

A
  • Epithelium: initially transitional (at the proximal end - near bladder), then becomes pseudostratified columnar epithelium, then stratified squamous, non-keratinizing near external opening (distal end)
  • lamina propia: Fibroelastic
  • Submucosa: contains erectile tissue
  • endodermally-derived
  • Common passage for urine and semen
230
Q

Components of the male reproductive system

A
  • Testis: Exocrine (spermatozoa from seminiferous tubules) Endocrine (testosterone from leydig cells)
  • Genital ducts: Intra or extra-testicular functions (vas deferens)
  • Accessory genital glands: exocrine (prostate)
  • Penis: Semen delivery and urine conduit
231
Q

Testis

A
  • Surrounded dense irregular C.T. capsule (= Tunica Albuginea; thick and collagen rich)
  • Septae (dense irregular C.T) divides testicular tissue into lobules
  • Lobules consist of:
232
Q

Male Germ Cell Development = Spermatogenesis

A
  • Spermatogenesis is more efficient at slightly lower than the core body temperature (35 °C)
  • Occurs from basal to luminal across the Seminiferous Epithelium
  • Developing germ cells contact each other with cytoplasmic bridges, and contact Sertoli cells via specialized cell-cell junctions (modified adherent junctions)
    a) Spermatogonia to
    b) Spermatocytes to
    c) Spermatids to
    d) Spermatozoa
233
Q

Intratesticular Ducts

A

1) Rete Testis:

2) Ductuli Efferentes:

234
Q

Extratesticular Ducts

A

1) Epididimyis:
2) Ductus/Vas Deferens:

3) Ejaculatory Ducts: passive flow of spermatozoa( no smooth muscle) andsemina lfluid from
vas deferense to urethra; epithelium similar to epididymis and ductus deferens. Passes through the prostate.

235
Q

Accessory Genital Glands

A

-Exocrine glands that provide the majority of the volume of the semen
-Have smooth muscle in stroma that contracts in response to sympathetic nervous system
stimulation as part of ejaculatory process

236
Q

Seminal Vesicles:

A

-Secret fructose-rich seminal fluid energy source for spermatozoa; majority of semen volume

237
Q

Cowper’s (Bulbourethral) Glands

A
  • Secrete G.A.G/ sialic acid-rich fluid

- lubricating

238
Q

Prostate Gland

A
  • Surrounds ejaculatory ducts and the urethra
  • Compound tubuloalveolar exocrine gland
  • Consists of Paranchyma (functional; epithelial), and stroma (supportive; connective tissue) Parenchyma
  • Secrete proteases into apical lumen, which has an important role in keeping sperm from bundling together-liquifies semen (‘PSA’ is one such protease and it is an important marker for detecting prostate cancer).
239
Q

Benign (not malignant) Prostate Hyperplasia

A

o Increased epithelial proliferation

o Hyperplastic epithelium remains correctly polarized; PSA secreted into lumen o Testosterone-dependent

240
Q

Prostate Carcinoma (‘carcinoma’=epithelially-derived cancer with potential to metastasize):

A

o Increased epithelial proliferation
o Loss of polarization and disruption of exocrine tissue architecture (eg. loss of apical lumina
of the exocrine gland); can lead to a pathologic epithelial-to-mesenchymal (EMT) transformation that makes the cells migratory and invasive
- which makes the tumor cells resistant to ‘anti- androgen’ therapy

241
Q

Penis

A
  • Contains:
  • > Urethra
  • > Erectile Tissue
  • > Helicine arteries
242
Q

Erectile Tissue

A
  • Corpora =columns of erectile tissue
  • Consist of highly vascular fibroelastic C.T (elastin) surrounded by an outer sleeve of dense
    irregular connective tissue (= tunica albuginea)
243
Q

Helicine arteries

A
  • Tunica media: very thick due to large amounts of smooth muscle
  • smooth muscle relaxes when stimulated by the parasympathetic nervous system
244
Q

Stomach Cells

A
  • Surface lining cell
  • regenerative cell
  • Mucous neck cell
  • Oxyntic parietal cell
  • Zymogenic chief cell
  • Enteroendocrine DNES/APUD cell
245
Q

Zymogenic chief cells

A
  • secrete zymogens apically into lumen
  • Zymogens are secreted in an inactive form that are then activated by the acid environment in the lumen of the stomach
  • Lots of RER.
246
Q

Enteroendocrine cell DNES

A

Secrete Hormones and Paracrine factors like:

  • VIP -> increases pertistalsis of intestine- endocrine
  • Gastrin -> increases parietal cell acid seretion and relaxes pyloric sphincter- paracrine
247
Q

Division between the rectum and anus

A
  • marked by the sharp transition of the mucous membrane from one bearing a columnar epithelium to one bearing a stratified squamous epithelium (can also undergo metaplastic change as occurs at gastro-esophageal junction) = Epithelial Transition
248
Q

Pectinate line

A

normally not functionally important, but is a site where congenital malformations can occur early in development as it is the site where epithelia from the endoderm (interal GI tract/tube) and the ectoderm (external anal/skin) fuse.

249
Q

2 Anal Sphincters

A
  • The more superior internal sphincter smooth muscle and is under involuntary/autonomic control - External sphincter is skeletal muscle and is under voluntary motor control.
250
Q

Hemorrhoids

A
  • Hemorrhoidal veins are swollen and can bulge into the rectoanal canal.
  • often caused by poor venous return to the hepatic portal vein and can be exacerbated by hepatic portal vein hypertension (ie. blockage) caused by, for example, liver cirrhosis
251
Q

Type I diabetes

A
  • occurs as a result of a decrease in functional ß cells (in the endocrine islets) which causes a decrease in insulin production
252
Q

Type II diabetes

A
  • often a decrease in responsiveness of target cells to insulin.
253
Q

zymogens

A
  • activated by acid hydrolysis when they reach the duodenum where the pH is low due to gastric secretions
254
Q

Acinar cells

A

= zymogenic cells

  • > Dark/chromophilic with H&E staining (L.M.)
  • > Large vesicles (E.M.)
  • > Secrete digestive enzymes in their inactive form = zymogens (proteases, carboxydases,
    lipases) ;
255
Q

Centroacinar Cells

A
  • > Pale/chromophobic with H&E staining (L.M.)
  • > No large secetory vesicles, many tight junctions between cells (E.M.)
  • > Secrete bicarbonate ions = prevent activation of zymogens until they reach the duodenum
256
Q

Dual blood supply into the liver via:

A
  1. The hepatic artery – Oxygen-rich blood from abdominal aorta
  2. Hepatic portal vein – Nutrient rich (drains the GI tract) and bilirubin pigment-rich (also drains
    spleen)
  3. Hepatic vein drains hepatic artery and hepatic portal vein (from GI) to the inferior vena cava
257
Q

Blood movement in the liver

A
  • blood from the hepatic artery and the portal vein mixes in the hepatic venous sinusoids (distended, open capillaries) that run between the hepatocytes within defined clusters of these cells (= hepatic lobule;)
  • the blood then drains into the central veins of the lobules
  • central veins then coalesce and exit the liver via the hepatic veins.
  • The venous sinusoids of the liver are patrolled by Kupffer cells which are resident macrophages
258
Q

Sinusoidal/Basal Domains of Hepatocytes

A
  • nutrient uptake

- endocrine release of Plasma proteins and Lipoproteins into the nearby venous sinusoids

259
Q

Billiary/Apical Domains of Hepatocytes

A

– exocrine release of bilirubin and bile salts/cholesterol into the bile canaliculi (very small passages that drain to bile ducts which have a simple cuboidal epithelial lining)

260
Q

Billirubin

A
  • used by the liver to make bile
  • produced in the spleen when RBCs are
    broken down (breakdown of the heme).
261
Q

Bile

A
  • generated by Hepatocytes
  • the finished bile product is transported to the gall bladder (for concentration and storage) before it is released into the duodenum where it emulsifies (breaks up) fat/lipid
  • this facilitates digestion/breakdown of lipids by lipases produced by the exocrine pancreas.
262
Q

The Gall Bladder Response to a fatty meal:

A
  • DNES/enteroendocrine cells in the mucosal epithelium of the small intestine release cholecystokinin (CCK) that:
    1. binds to CCK receptors on the smooth muscle cells of the sphincter Oddi and causes them to relax
    2. CCK stimulates sm. muscle in the muscularis of the gall bladder to contract
  • together these two actions cause bile to be released into the small intestine (at the same time CCK stimulates pancreatic enzyme/zymogen secretion by acinar cells also)
263
Q

Gall Stones

A
  • caused by bile salt and cholesterol precipitation in draining bile duct
264
Q

Main functions of the kidney:

A
  1. Production of glomerular filtrate from the blood (in cortex)
  2. Modify the filtrate to produce urine (in both cortex and medulla)
265
Q

The function unit of the kidney

A

uriniferous tubule which consists of the nephron and the collecting tubule

266
Q

Glomerular filtrate

A
  • contains high concentrations of water, ions, glucose, and urea.
  • very similar to plasma in composition except it lacks plasma proteins
  • contained in the urinary space
267
Q

Bowman’s Capsule

A
  • continuous simple squamous epithelium with tight junctions = parietal layer
  • inside the capsule are glomerular capillaries
268
Q

Glomerular Capillaries

A

o Tuft of fenestrated capillaries

o Covered by specialized cells = Podocytes = visceral layer of Bowman’s capsule

269
Q

Vascular Pole

A

o Afferent (to) arterioles: brings blood into the corpuscle
o Efferent (away) arterioles: takes blood out of the corpuscle (becomes the
peritubular capillary network that surrounds modifying tubules and collecting
tubules in the kidney cortex and the medulla)

270
Q

Glomerular Filtration Barrier

A
  • 3 levels of filtration
    1. Fenestrations(fenestrated capillary endothelium): allows free passage of molecules/water
    2. Basal lamina: prevents passage of molecules larger than 70 KDa
    3. Slit Diaphragms: located between the pedicels from the podocytes prevent movement of anionic plasma proteins by charge repulsion due the presence of proteoglycans on the surface of the pedicels of the podocytes surface
271
Q

Descending limb of the loop of Henle

A
  • Descends into the medulla
    -This region is highly water permeable (has aquaporins water channels in the cell
    membrane) some water moves out of the lumen into the peritubular connective
    tissue following the salt that is in the peritubular connective tissue of the medulla
272
Q

Ascending limb of the loop of Henle

A
  • No aquaporins in the membrane; therefore is water impermeable
  • Lots of tight junctions
  • As limb ascends, transitions into more cuboidal (thicker) epithelium
  • NaCl is actively pumped into the peritubular connective tissue of medulla which
    helps establishes osmotic salt gradient to withdraw water from descending limb as described in A. above (and from collecting tubules in the anti-diuretic state
273
Q

Renin

A
  • secreted in response to gap junction-mediated communication by juxtaglomerular cells
  • secreted into the blood of the arterioles of the vascular pole of the renal corpuscle.
  • initiates the angiotensin cascade that stimulates the release of aldosterone (from the zona glomeruloa of the adrenal cortex) and ADH/ Vasopressin (from the posterior pituitary)
    to decrease urine volume (= the ‘anti-diuretic’ state)
274
Q

Aldosterone

A
  • stimulates NaCl pumps of the ascending loops of Henle and medullary portions of the distal tubule - this increases the salt concentration in the medulla
275
Q

ADH/Vasopressin

A
  • elevates water permeability of the collecting tubules due to insertion of aquaporin water channels in plasma membrane
  • causes the water to flow out of the tubules into the particular connective tissues
276
Q

External Sphincter of the Bladder

A

skeletal muscle (voluntary) that wraps around proximal urethra (relaxes to allow urination)

277
Q

Internal Sphincter of the Bladder

A
  • smooth muscle (involuntary) that relaxes for urination
278
Q

Lobules of the testis consist of:

A

a) Loose C.T. that is highly vascularized
b) Leydig cells:
c) Seminiferous tubules:

279
Q

Loose CT of the testis

A
  • Many fenestrated capillaries

- contains clusters of Leydig cells within the C.T

280
Q

Leydig cells of the testis

A
  • Organized in clusters and are major endocrine cells

- producing testosterone in response to leutinizing hormone (LH)

281
Q

Seminiferous tubules of the testis

A
  • Contain myoid cells on the outside: slightly contractile fibroblasts
  • Contain Sertoli Cells:
  • Supportive cells for developing germ cells (spermatozoa)
  • Form a simple columnar epithelium
  • There are basally located tight junctions between them that form the blood-testis barrier
282
Q

Production of testosterone

A
  • LH receptors are cell surface G-protein coupled receptors that generate cAMP as a 2nd messenger
  • cAMP activates protein kinases that activate esterases that cleave estrified cholesterol in lipid droplets into free cholesterol
  • This is converted to pregnenolone in the mitochondria which is then shuttled back and forth between smooth ER and mitochondria via lipid transfer proteins; finally converted to testosterone in SER
  • Prominent SER comes into close contact with mitochondria at ER junctions
  • Testosterone secreted into loose C.T. picked up by fenestrated capillaries and Sertoli cells
283
Q

Blood-testis barrier

A
  • formed by tight junctions on the basal side of the seminiferous tubules
  • provides immunoprotection for germ cells that develop on the adluminal side of the junctions in the seminiferous tubules
284
Q

Spermatogonia

A
  • diploid stem cells
  • respond to testosterone by proliferating and sending cells down the spermatogenic lineage
  • not behind the blood-testis barrier
  • basally located
285
Q

Spermatocytes

A
  • migrate across tight junction to the luminal side of the blood-testis barrier
  • undergo meiosis (haploid)
  • start to express novel cell surface antigens and therefore are immunoprotected to prevent an autoimmune response
286
Q

Spermatids

A
  • develop near or at luminal surface of Sertoli cells

- undergo morphological differentiation to generate spermatozoa

287
Q

Spermatozoa

A
  • Have head containing condensed haploid DNA and digestive enzyme containing lysosomal enzymes
  • neck contains centrioles that generate microtubules that extend into the tail
  • middle piece contains mitochondria to generate ATP for motility (by bending microtubules organized into the ‘axoneme’ in the tail)
  • Not motile in seminiferous tubules
  • Released apically into the tubule lumen with serous/liquid secretions of Sertoli cells
  • Not motile when released
288
Q

Rete Testis

A
  • Continuous with seminiferous tubules
  • Collect spermatozoa and serous fluid and move them passively (bulk flow due to Sertoli cell secretions and myoid cell contractions that
    surround seminiferous tubules) outward to ductuli efferents
  • Lined by simple cuboidal epithelium
  • Moves through dense irregular C.T. of the capsule (tunica albuginea)
288
Q

Ductuli Efferents

A
  • Collect material from rete testes and moves it into epididymis actively (although weakly)
  • Lined by a simple epithelium of varying heights (ie. has a ‘scalloped’ appearance)
    i. Clusters of low cuboidal cells that are resorptive (initiates flow out of tubules)
    ii. Interspersed with clusters of tall ciliated columnar cells (coordinated ciliary beat increases flow out of tubules)
  • Thin layer of smooth muscle generates has some peristaltic contractility
288
Q

Epididimyis

A

o Stores and modify spermatozoa
o Spermatozoa become slightly motile (become fully motile in female
reproductive tract
o Pseudostratified columnar epithelium
i. Basally located stem cells
ii. Columnar principle cells that have stereocilia (long non-motile
microvilli- actin core) to increase surface area and aid in absorption of
excess fluid and phagocytocis of excess spermatozoan cytoplasm
iii. Circular layer of smooth muscle- initiates pulsatile, non-peristaltic
ejaculatory contractility

288
Q

Ductus/Vas Deferens

A

o Transports spermatozoa during ejaculation
o The epithelium is the same as epididymis (pseudostratified columnar)
o Has thick multi-layered smooth muscle in adventitia
• The muscle is under the control of sympathetic stimulation, which is key to the ejaculatory contraction. This results in a powerful, rhythmic and short-lived ejaculation

288
Q

metastasis

A
  • ability to form new tumours at secondary, distant sites
288
Q

Assessment of Prostate Carcinoma

A

o PSA released into stroma/fenestrated capillaries (ie. facilitates increased PSA in serum which can be assessed clinically and can be used for screening and/or as a measure of treatment response (i.e. there will be decreased PSA levels as tumor shrinks) or a relapse (i.e. increased PSA levels as tumor enlarges)

288
Q

How Viagra Works:

A
  • preventing the breakdown of cGMP and therefore potentiates and makes the erectile response more long-lived that is initiated by the parasympathetic nervous system.
288
Q

Erection

A
  • parasympathetic autonomic stimulation causes:
  • > relaxation of the smooth muscle = increased blood flow into venous sinuses (thinned-walled venous sinusoids/enlarged capillaries) within the corporal fibroelastic tissue
  • > production of Nitric Oxide which facilitates the helicon smooth muscle relaxation by producing the second messenger cGMP
288
Q

Flaccid state

A
  • blood from helicine arteries is shunted directly to veins and outside the erectile tissue and therefore bypasses the venous sinuses
288
Q

Anastomoses

A
  • blood going directly from arteries to veins without an intervening capillary bed
288
Q

Vasectomy

A
  • surgical disruption by various means
  • Ductus deferens is clipped to disrupt passage of spermatozoa and seminal fluid produced by Sertoli cells
  • no hormonal disruption and spermatozoa are still produced
  • Epithelial cells become highly phagocytic to resorb spermatozoa and seminal fluid
  • In the rare event spermatozoa escapes into wall of vas deferens, inflammation can occur due to immune response
299
Q

Autocrine

A

cells secrete a hormone that acts on the same cell

300
Q

Paracrine

A

cells secrete a hormone that targets nearby cells

301
Q

Endocrine

A

cells secrete a hormone that travels a great distance to target multiple cell types and organs

302
Q

Peptide Hormones

A
  • Composed of amino acids arranged as a complex chain or a simple string. e.g. oxytocin is a peptide that consist of 9 amino acids.
  • Peptides are water soluble (= hydrophilic)
303
Q

Amine Hormones

A
  • Monoamines: composed of one amino group connected to an aromatic ring. e.g. adrenaline is derived from the single amino acid tyrosine
  • Thyroid hormone: derived from 2 amino acid (tyrosine) residues. It is bound to transport proteins in the blood.
  • Most amines are water soluble (=hydrophilic), some are lipid soluble (=lipophilic; e.g.
    thyroid hormone)
304
Q

Steroid hormones

A
  • Composed of a core of 4 fused carbon rings and 1 side chain
  • functional groups (eg. hydroxyl groups) attached to these rings determine activity Steroids are lipid soluble (=lipophilic)
305
Q

Water soluble/ hydophilic hormones

A
  • bind to cell surface membrane receptors and initiate intracellular signal transduction cascades that can have many functional outcomes within
    the cell, including changing gene expression.
306
Q

lipid soluble/lipophilic hormones

A
  • thyroid hormone and all steroids
  • bind intracellular receptors (mostly cytoplasmic when not bound to hormone) that translocate to the nucleus following hormone binding and affect gene transcription directly (eg. can act as transcription factors)
  • free to enter the brain and regulate all forms of function within the entire CNS
  • bind to carrier plasma proteins to ensure solubility in the blood
307
Q

Pituitary

A
  • Has 2 major lobes
    • The pituitary secretes 9 hormones
    • The lobes of the pituitary are physically linked to the hypothalamus by the median eminence
    • The pituitary provides a link between the brain and the periphery (ie. tissues of the body), by two different pathways:
    1. Direct Pathway
    2. Indirect Pathway
308
Q

Anterior pituitary

A
  • contains several different secretory non-neuronal cell types
  • each of which synthesizes and secretes a unique stimulating hormone that act acts on other endocrine organs (eg. ACTH) or a factor that acts on other tissues (eg. Growth Hormone).
  • different cell types in the anterior pituitary are regulated by the secretions of different hypothalamic nuclei.
  • the anterior pituitary is epithelial
  • Formed by invagination of ectoderm in the oral cavity during development, migrates superiorly
  • pinches off to become ‘Rathke’s Pouch’ at 5 weeks of development
  • At 8 weeks Rathke’s pouch completely pinches off, and pituitary gland finishes development at 12 weeks.
  • Made up of cords of hormone-secreting (endocrine) epithelial cells that are differentially stained by H&E
309
Q

Posterior Pituitary

A
  • contains the axon terminals of neurosecretory cells that release peptide hormones (AVP/ADH or OT) that are synthesized in the neuronal cell bodies that are located in the hypothalamus.
  • neural in nature
  • Formed from the ventral extension of the brain
310
Q

Direct Pathway

A
  • Involves the posterior pituitary
  • peptide hormones are synthesized in the cell bodies of neurons in the hypothalamus (ie. within hypothalamic ‘nuclei’ = clusters of nerve cell bodies):
  • in the paraventricular nuclei (PVN) and in the supraoptic nucleus (SON) of the hypothalamic nuclei
  • hormones are then transported down axons that pass through the median eminence.
  • hormones are then stored in vesicles in axon terminals (=Herring Bodies) in the posterior pituitary.
  • Upon appropriate stimulation, the hormones are released by exocytosis and are then able to move into nearby capillaries that drain into the hypophyseal vein for distribution to the tissues of the body.
311
Q

Indirect Pathway

A
  • Involves the anterior pituitary
    • ‘Releasing’ peptide hormones are synthesized in nerve cell bodies in the hypothalamus (ie.
    within hypothalamic nuclei).
  • then travel down axons to terminals in the median eminence where they are released and are picked up by fenestrated ‘primary’ capillaries that drain into the hypophyseal portal venules.
  • hypophyseal venules drain into secondary fenestrated capillaries located in the anterior pituitary where the releasing hormones exit the blood and stimulate the production of ‘stimulating’ peptide hormones by endocrine cells of the anterior pituitary
  • then enter the capillaries for distribution to tissues (ie. other endocrine glands of the body.
  • can lead to a huge increase in molar production of the ultimate hormone generated in the periphery
312
Q

Chromophobic cells

A
  • Stain weakly because they contain few secretory granules/vesicles
  • Function is unclear but likely gave a supportive function; can secrete factors that act as paracrine factors (eg ‘Folliculostellate’ cells
  • found in the anterior Pituitary
313
Q

Chromophilic cells

A
  • Stain intensely because they contain a high number of secretory granules/vesicles that contain hormones. Eg. Gonadoropes, which makes FSH and LH under the regulation of GnRH.
    • Acidophils: vesicles react to acid dyes and stain PINK (bind eosin)
    • Basophils: vesicles react to basic dyes and stain BLUE (bind hematoxylin)
  • found in the anterior pituitary
314
Q

Pituicytes

A
  • neuroglial in nature
  • physical & nutritive support (ie. do not release hormone)
  • found in the posterior pituitary
315
Q

Nervous Material

A
  • Terminal neuronal swellings (=Herring bodies) derived from axons whose nerve cell bodies originate in the nuclei of the hypothalamus
  • Herring bodies are packed with secretory vesicles for the storage and subsequent secretion of peptide hormones (eg. AVP and OT); therefore, hormones secreted from here by the usual vesicle fusion mechanism.
  • found in the posterior pituitary
316
Q

Minor Intermediate Lobe of Pituitary

A
  • Same embryonic derivation as anterior pituitary
  • Rudimentary structure in humans, representing <1% of the total pituitary gland mass in adults
  • Larger during fetal life (representing ~3.5% total pituitary gland mass) and in lower vertebrates
  • Secretes melanocyte stimulating hormone (MSH), which brings about changes in skin colour
317
Q

Pituitary stalk interruption syndrome

A
  • Truncated or absent pituitary stalk and a small sella turcica Decreased hormone secretion such as LH/FSH/Testosterone
318
Q

Thyroid Gland

A
  • Derived from endoderm (as a downgrowth of the pharynx)
  • Consists of functionally distinct units with different modes of secretion and secretion products:
    1. Follicular unit
    2. Parafollicular Cell (“C” cell) Clusters
319
Q

Follicular Unit

A
  • Made up of follicular epithelial cells that synthesize, store, secrete and modify thyroid hormones
  • Responds to TSH (produced by thyrotrophs) produced in the anterior pituitary
  • produce thyroid hormones (= T3 and T4; a.k.a ‘thyroxine’)
  • secrete iodinated thyroglobulin (a T3/T4 precursor) secreted apically into the central colloid space of the follicle
  • later iodinated TGB is endocytosed and processed into T3/T4 that is released basally into the connective tissue to be picked up by fenestrated capillaries so that it can be transported to distant organs (eg. as hormones).
320
Q

Parafollicular Cell (“C” cell) Clusters

A
  • Small clusters of endocrine epithelial cells located in the loose connective tissue between follicles
  • Respond to high plasma calcium levels by secreting the hormone calcitonin, which is a peptide hormone that inhibits the release of Ca2+ from bone by decreasing osteoclast activity in bone and decreasing calcium absorption by intestinal epithelium, thereby lowering plasma calcium levels (functionally, it antagonizes the action of parathyroid hormone)
  • releases calcitonin basally into the connective tissue
  • calcitonin is then picked up by fenestrated capillaries for travel in the plasma to distant sites (ie. classical endocrine gland structure/function).
321
Q

Parathyroid glands

A
  • 4 different glands
  • Buried in the posterior aspect of the thyroid gland; but histologically & functionally distinct from it (ie. surrounded by thin connective tissue capsule).
  • Derived from endoderm.
  • Consists of two cell types arranged haphazardly in clumps and cords (therefore easy to recognize amongst more organized follicles of the thyroid):
    1. Oxyphil cells
    2. Chief cells
322
Q

Oxyphil Cells

A
  • inactive, non-secretory cells
323
Q

Chief cells

A
  • Chromophilic due to secretory vesicles
  • Respond to decreases in circulating calcium levels
  • Secretes PTH (parathyroid hormone),
324
Q

Parathyroid Hormone (PTH)

A
  • a peptide hormone, that acts on target organs, including bone to activate osteoclasts and thereby liberate calcium from the inorganic portion of the matrix.
  • stimulates the intestinal epithelium to increase calcium absorption and the kidneys to increase reabsorption; the net effect is an increase in plasma calcium levels.
325
Q

Thyroid Gland

A
  • Composed of follicles (follicular epithelial cells surrounding the central, luminal colloid) and parafollicular C cells.
  • Follicular cells respond to TSH (produced by ‘thyrotrophs’ in the ant. pituitary) to
    secrete iodinated thyroglobulin (a T3/T4 precursor) secreted apically into the central colloid space of the follicle; later iodinated TGB is endocytosed and processed into T3/T4 that is released basally into the connective tissue to be picked up by fenestrated capillaries so that it can be transported to distant organs (eg. as hormones).
326
Q

Thyroid Hormone Synthesis

A
  • Stimulated by TSH from the anterior pituitary which binds to TSH receptors on
    the basal surface of the follicular epithelial cells.
  • Thyroglobulin (=TGB, not to be confused with thyroxine-binding globulin = TBG) -> synthesis occurs in the RER and it is then modified in both the RER and Golgi.
  • Vesicles containing TGB are then transported from the trans Golgi network to the
    apical plasma membrane of the follicular cells, where their contents are released
    into the colloid.
327
Q

Thyroid hormone storage

A
  • Iodine (actually reduced to form ‘iodide’ ion = I-) is actively taken up from the
    bloodstream (source: absorption from food intake) by symporters at the basal surface the follicular epithelial cells.
  • Iodide is transferred to the apical membrane of the follicular cells where it is covalently linked to tyrosine amino acids of TGB just as the latter is released into the colloid.
  • linkage is carried out by ‘thyroid peroxidase’ an enzyme that is located in the apical follicular cell membrane (ie. TGB release and iodination at the apical membrane/colloid interface occur simultaneously and then the iodinated thyroglobulin is stored in the central colloid rather than in the follicular cell; this is unique amongst all endocrine glands).
  • A single iodination of one TGB tyrosine residue results in the formation of monoiodinated tyrosine (MIT) whereas two iodionations results in the formation of diiodinated tyrosine (DIT). The coupling of one MIT and one DIT results in the formation of one triiodothyronine (T3), whereas the coupling of two DITs results in the formation of one tetraiodothyronine (T4 = thyroxine).
328
Q

Thyroid Hormone Release

A
  • Also stimulated by TSH which causes endocytosis of iodinated TGB back into the follicular epithelial cells.
  • Endocytic vesicles fuse with endosomes the iodinated TGB is digested by proteolytic enymes which generates free T3 and T4.
  • T3 and T4 are released at the basal plasma membrane of the follicular cells where they enter T3/T4 enter the connective tissue spaces of the thyroid gland and then pass through pores in fenestrated capillaries to enter the bloodstream.
329
Q

T3 vs T4

A
  • 90% of the thyroid hormone released by follicular cells is T4. T4 has an increased affinity for the thyroxine-binding globulin (TBG =carrier in plasma protein) and target cells can readily convert T4 to T3.
  • Free T3 and T4 within cells can bind thyroid hormone receptors within target cells and thus affect gene transcription. Of note, T3 has a higher affinity for these receptors (which explains its higher biological activity in the target cells).
330
Q

Adrenal Gland

A
  • composed of a cortex (outer portion of gland) and a medulla (inner portion of the gland)
331
Q

Cortex of the adrenal Gland

A
  • mesodermally-derived
  • divided into 3 zones whose cells express different enzymes that modify cholesterol to produce different steroid hormones
    1. Zona Reticularis
    2. Zona Fasciculata
    3. Zona Glomerulosa
332
Q

Zona Reticularis

A
  • clusters of of cells on inner aspect of adrenal cortex, produce and secrete weak androgens (eg. DHEA)
333
Q

Zona Fasciculata

A
  • Tall columns of cells in central aspect of adrenal cortex, produce and secrete glucocorticoids (eg. cortisol) under the control of ACTH from the anterior pituitary
334
Q

Zona Glomerulosa

A
  • small, spherical nests of cells in the outer portion of the adrenal cortex, produce and secrete mineralocorticoids (eg. aldosterone; stimulated by angiotensin II generated, in part, in kidney)
335
Q

hypothalamic/pituitary/adrenal axis is regulated by:

A
  • negative feedback.
  • Increased levels of cortisol signal the PVN to inhibit CRH production, which, in turn, decreases ACTH production by the anterior pituitary.
336
Q

Medulla of the Adrenal Gland

A
  • neuroectoderm-derived
  • Contains chromaffin cells
  • Cells of the medulla produce catecholamine hormones (eg. epinephrine)
337
Q

Cortical regions of the adrenal gland

A
  • stores cholesterol and steroids in prominent lipid droplets.
  • where steroid hormone synthesis occurs
  • have prominent smooth ER and the mitochondria and many ER junctions (lipid transfer proteins help move the steroid precursors between these two compartments where the enzymes are located that modify them).
  • The christae of mitochondria have characteristic tubulo-vesicular shapes which are an excellent diagnostic on transmission electron micrographs.
  • Chromaffin cells of the adrenal medulla synthesize and secrete amines
338
Q

Thyriod axis regulation

A
  • negative feedback of T3/T4
  • Increased levels of T3/T4 signal to the PVN to inhibit further production of T3/T4 by suppressing TSH release. Insufficient feedback (deficient iodine, decreased T3/T4 release) results in an abnormal enlargement of the thyroid gland (goiter) due to excessive secretion of TSH which contstantly stimulates the follicular cells.
339
Q

Chromaffin cells

A
  • modified postganglionic sympathetic in the adrenal medulla
  • neurosecretory cells that lack dendrites and axons
  • Stimulated by pre- ganglionic sympathetic nerves whose cell bodies are located in the ventral horns of the thoracic portion of the spinal chord which travel to the adrenal medulla without first synapsing in a peripheral ganglion
  • synthesize and secrete amines that are stored in classical membrane-bound secretory vesicles/granules that undergo exocytosis when stimulated
340
Q

Catecholamines

A
  • secreted in response to stimulation by preganglionic sympathetic nerves.
341
Q

Steroid Synthesis

A
  • begins as cholesterol

- occurs via enzymes found in both mitochondria and smooth ER which are often in close proximity.

342
Q

Germinal Epithelium of the Ovary

A
  • simple cuboidal epithelium that covers the surface of the ovary (and is disrupted/torn such that it must heal with each ovulation; thus has many many stem cells)
  • can give rise to benign ovarian cysts if a portion of the wounded epithelium gets trapped within the ovary
  • the source of some ovarian carcinomas (along with the epithelium that line the fimbrae and distal/final portion of the oviduct).
343
Q

Ovarian Cortex

A
  • contains the ovarian follicles (up to 1 million at birth, only ~400 fully develop during reproductive period from puberty to menopause)
  • outermost layer of cortexis: dense irregular connective tissue (often called the ‘tunica albuginea’)
  • inner layer: loose connective tissue
344
Q

Medulla of the Ovary

A
  • loose connective tissue

- contains many large blood vessels, nerves and lymphatics

345
Q

Follicullar Phase of the ovarian cycle

A
  • Day 1- 14 of ovarian cycle
  • 20- 50 primordial follicles begins to develop which develops into the primary follicle, unilmainar to the primary follicle, multilaminar to the secondary follicle to the graafian follicle which is ovulated
346
Q

follicular cells

A
  • surround the primary oocyte
  • start as a single layer of squamous epithelial cells around the primordial follicle
  • become a single layer of cuboidal cells (activated) in the primary follicle, unilaminar
  • become stratified cuboidal (=Granulosa Cells) in the primary follicle, multilaminar
  • remain surrounding the oocyte
347
Q

In the primary follicle

A
  • Zona pellucida forms
  • follicular epithelial cells become ‘granular’ = granulosa cells
  • Theca interna forms
  • the outermost stromal condensation of ‘theca externa cells’ that are both contractile and able to deposit collagen fibers to give structure to the developing follicle
  • initiated by FSH.
348
Q

Zona Pellucida

A
  • glycoprotein layer that forms around the primary oocyte

- prevents polyspermy and cross-specis fertilization

349
Q

Granulosa cells

A
  • stratify/multilayer to form multilaminar primary follicles that are surrounded by a basement membrane
  • produce estrogen from androstendione via the aromatase enzyme located in the sER
  • granulosa cells are not able to synthesize androstenedione themselves
  • during the luteal phase they produce progesterone because they can get cholesterol
350
Q

Theca interna

A
  • cells outside the basement membrane stromal / mesenchyme-like condense to form the theca interna
  • well-vascularized
  • take up cholesterol
  • produce small amounts of progesterone (and release it for uptake by the vascular system)
  • produce androstendione which is released and diffuses across basement membrane to enter the avascular granulosa cells
  • during the luteal phase they produce large amounts of androstendione because they are able to take up more cholesterol
351
Q

In the Secondary Follicle

A
  • Fluid-filled spaces = ‘antra’ form contain steroid hormones and locally acting factors
  • driven by FSH.
352
Q

Graafian Follicle

A
  • Multiple antra coalesce into one very large antrum that surrounds the primary oocyte and the corona radiata
  • only one Graafian Follicle becomes dominant probably due to high estrogen (the lagging/stalled follicles subsequently die = ‘atresia’)
353
Q

Ovulation

A
  • At ~Day 14 a surge of LH causes ovulation to occur
  • greatly facilitated by the contraction of theca externa cells
  • the primary oocyte with attached zona pellucida and corona radiata are released into pelvic cavity where they are ‘caught’ by the fimbria that bring the structure into the oviduct
  • the primary oocyte undergoes the first meoitic division to generate the secondary oocyte (the 2nd meiotic division is not completed until/if fertilization occurs)
354
Q

Luteal Phase of Ovarian Cycle

A
  • Day 14-28 of the ovarian cycle
  • the corpus luteum forms
  • High steroid production which feeds back on both the hypothalamus and the anterior pituitary to greatly reduce decrease first FSH and, later, LH production by the anterior pituitary
  • if there is no fertilization/embryonic development there is no hCG production and the corpus luteum degenerates into the corpus albicans
  • If hCG is produced by developing embryo/fetus the corpus luteum is maintained for the first 8-12 weeks of pregnancy until the placenta fully differentiates and itself produces steroid hormones
355
Q

Corpus Luteum

A
  • formed by the portion of the mature follicle (without the oocyte) that remains in the ovary
  • the granulosa and theca interna cells ‘luteinize’ (fully differentiate; fill with lipid droplets containing cholesterol esters; fully develop their SER mitochondria and intervening ER junctions)
  • produce large amounts of steroid hormones that are important for preparing/maintaining uterine lining for implantation of the embryo.
  • the corpus luteum degrades into the corpus albicans if there is no hCG production
  • the corpus luteum is maintained for 8-12 if there is production of hCG
356
Q

Steroid production during the follicular phase

A
  • vascularized theca internal cells take up cholesterol and produce progesterone and produce androstendione which is released
  • follicular/granulosa cells which can convert it into estrogen
  • estrogen released by follicular/granulosa cells and diffuse back across the basement membrane to be picked up by capillaries
357
Q

Steroid production during the Luteal Phase

A
  • there is a breakdown of the basement membrane as the theca interna and granulosa cells luteinize;
    blood vessels now present in both compartments.
  • there is now a large production of progesterone and estrogen from the granulosa cells (because the theca lutein cells can produce large amounts of androstenedione)
    -Therefore, while both cell types produce large amounts of steroid
358
Q

Uterus

A
  • the wall has 3 layers (inner to outer)
    1. Endometrium
    2. Muscularis/myometrium
    3. Serosa
359
Q

Endometrium of the Uterus

A

= mucosa
- simple columnar epithelium with simple tubular
glands that secrete nutrients and loose connective tissue (= lamina propria)
- has 2 parts:
1. Functional layer
2. Basal layer

360
Q

Functionalis

A
  • the functional layer of the endometrium of the uterus
  • Thick superficial/apical layer that is sloughed off into the lumen of uterus at menstruation
  • reforms during proliferative phase of menstrual cycle
  • differentiates during the secretory phase
  • supplied by the helical/spiral arteries that themselves are also reformed with each menstrual cycle
361
Q

Basalis

A
  • the basal layer of the endometrium of the uterus
  • Deep narrow layer with the basal portion of glands and connective tissue
  • remains after menstruation and contains stem cells that will move up into the functional layer during proliferative phase
  • supplied constantly by the straight arteries
362
Q

Muscularis/Myometrium of the Uterus

A
  • smooth muscle layer
  • Makes up 95% of the uterine wall
  • During pregnancy there is an increase in the size and number of smooth muscle cells, allowing the uterus to hold the fetus.
  • During labor, these cells are key in “pushing out” the baby. The contraction of these cells is controlled by the posterior pituitary via the release of oxytocin.
363
Q

Serosa of the Uterus

A
  • consists of a dense connective tissue adventitia convered by a simple squamous epithelium has apical proteoglycans (=mucins) that reduce the friction between the uterus and other pelvic organs that are also covered with a serosa
364
Q

Menstrual Cycle

A
  • consisits of 3 different phases:
    1. Menstrual phase (Day 1-4)
    2. Proliferative Phase (Day 4-14)
    3. Secretory Phase (Day 14-28)
365
Q

Menstrual Phase

A
  • Day 1-4
  • Day 1 is the first day of ‘bleeding’ (after estrogen and progesterone have fallen; continues until day 4)
  • Almost the entire functional layer of the uterine wall is lost; the basal layer remains including the base of the secretory glands and the straight arteries.
366
Q

Proliferative Phase

A
  • Day 4-14
  • Estrogen initiates re-growth/rapid proliferation of the functional layer (most stem cells actually reside in the basal layer and then move into the developing functional layer after they start to proliferate; surface epithelium reforms, the glands develop (are ‘straight/tubular’ and undifferentiated/non-secretory at this point.
  • Helical arteries re-form in the functionalis
367
Q

Secretory Phase

A
  • Day 14-28
  • Progesterone causes the functional layer to increase in size/thickness
  • Spiral arteries fully form to facilitate increased thickness
  • The glands fully differentiate and twist/become spiral or ‘sawtooth’ in appearance on
    histological sections; glycogen rich nutritive material is secreted into the ducts of the glands and it moves into the main lumen of the uterus where it is utilized by the fertilized egg/early embryo until the placenta forms.
368
Q

If fertilization doesn’t occur…

A
  • the embryo does not develop the corpus luteum begins to degenerate such that estrogen and, especially, progesterone levels fall .
  • causes the helical arteries to constrict which causes the functional layer die (i.e. the cells becomes ‘necrotic’), and menstruation begins.
369
Q

If fertilization occurs….

A
  • the developing embryo begins to produce hCG which maintains the
    corpus luteum through the first trimester of pregnancy until the placenta takes over that function.
370
Q

Mammary Glands

A
  • Each mammary gland consists of 15-20 exocrine glands = compound tubuloalveolar glands.
  • Parenchymal epithelium is derived from ectoderm (an invagination of the epidermis); is the functional, milk-producing, portion of the gland. It is estrogen, progesterone, prolactin and oxytocin sensitive and it is also the portion of the gland that gives rise to breast carcinomas
    (cancer)
  • Stromal connective tissue is mesodermally derived and it plays both an inductive and
    supportive function.
371
Q

Resting Mammary Gland

A
  • Parenchyma consists of ducts and terminal ductules that are clustered together as lobules
  • Terminal ductules consist of a simple cuboidal epithelium that is surrounded by a basket-like network of contractile myoepithelial cells (these are ectodermally-derived and are part of the
    epithelium, they are not muscle)
  • Stroma is loose connective tissue within the lobule and dense connective tissue in between the
    lobules. There is also some adipose tissue which increases with age.
372
Q

Pregnant and Lactating Mammary Gland

A
  • During early pregnancy estrogen and progesterone first drive proliferation of the parenchyma, branching of the ducts, and alveolar development within the terminal ductules.
  • During late pregnancy the alveolar epithelial cells differentiate and synthesize milk proteins, lipids and carbohydrate which are package together in vesicles that are transported to the sub- apical cytoplasm.
  • After birth prolactin stimulates secretion of milk by alveolar epithelial cells into the alveolar lumens
  • Infant suckling initiates oxytocin release which induces a contraction of the myoepithelial cells for milk ejection out of the alveoli and lobular ducts.

CAPS390 (2 decks)

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