BIOM Part 3 :) Flashcards

1
Q

What was Hippocrates theory?

A

Hippocrates postulated the “Humoral Theory” i.e. blood, phlegm, black
bile & yellow bile

  • Humoral Theory
    states that an imbalance in these factors causes
    disease e.g. yellow bile found in gall bladder & showed itself with
    jaundice
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What did Galen make?

A

Galen formalized the relationship between humoral medicine & Greek
natural philosophy
* The 4 humours are made up of 4 qualities (hot, cold, dry, & wet)
* Body humours & physical world elements shared a common qualitative
nature
* Microcosm (little world of human body) & macrocosm (greater world)
related to each other

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Before the 17th century, If unhealthy, key to restore balance is:

A
  1. Lifestyle (diet & exercise)
  2. Medication (herbs)

“Opposites cure opposites” e.g. cold remedy cures hot illness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How was illness seen before the 17th century

A

Illness seen as internal disorder of body, not the result of a specific agent like bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

When did humoral vision of body last until?

A

Humoral vision of body lasted until late seventeenth century in
Europe
* By middle ages this was seen as “quackery”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

New science of Galileo, Descartes, Newton, & Boyle replaced
Aristotelian

A

, qualitative, natural philosophy with a mechanical,
chemical, & mathematical vision of the world & body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Medicine before 17th century trends and dates:

A

1200-1500s
* Notions of pulmonary circulation
1600s
* Valves in veins
* Blood circulates body & is pumped by the heart
1658
* First description of red blood cells (RBCs) by a 21 year old microscopist
1661
* The capillary system
1665
* First recorded blood transfusion (dog to dog)
1667
* First human blood transfusion (lamb
to boy)
* Most failed because blood types hadn’t been discovered yet
1674
* Anton van Leeuwenhoek discovered that RBCs are 25,000 times smaller than a grain of sand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Medicine from 1700-1984

A

1700-1800s
* Transfusions still failing

1800-1900s
* Properties of blood emerge (coagulation
factors, platelets in clots, etc.)
* Successful human blood transplants

1917
* Red Cross organized civilian blood donor
service during WWI & II leading to new
developments in storing & using blood
* Optimized glucose-citrate solutions (prevent
coagulation & allow for viable storage)

1959
* X ray crystallography reveals hemoglobin
structure (protein in RBCs that carries oxygen)

1965
* Slowly thawing frozen plasma precipitated
factor VIII (antihemophilic factor) which has
great clotting power
* Adding factor VIII via replacement therapy
helps to stop & prevent bleeding

1971
* Hepatitis B discovered through infected donors

1981
* First cases of AIDS
* Hemophiliacs developed AIDS suggesting a
blood-borne component

1983 & 1984
* AIDS virus identified
* Patients infected with blood-borne pathogens
from transfusions led to screening & lawsuit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Functions of the circulatory system

A
  1. Transportation of all substance essential for cellular metabolism
    * Respiratory (RBCs)
    * Nutritive (digestive)
    * Excretory (waste)
  2. Regulation
    * Hormonal
    * Temperature
  3. Protection
    * From injury (clotting)
    * From pathogens (immune)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Hematopoiesis

A

Formation of blood cells
* Hematopoietic stem cells
originate in the embryo &
migrate to different tissues
Liver is the major
hematopoietic organ of the
fetus
* Bone marrow is the major
hematopoietic organ after birth
* Cytokines play important roles in hematopoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Blood samples after centrifugation

A

RBC
* Most abundant blood cells
* Biconcave disc shape
* Packed at the bottom

WBC, platelets
* Thin, light interface
* “Buffy coat”

Plasma fluid sits at the very top

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Hematocrit

A

% total volume of packed RBCs

Female: 35-46%
Male: 41-53%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Hemoglobin range

A

Hemoglobin (oxygen capacity of RBCs)

Female: 12-16g/100mL
Male: 13.5-17.5g/100mL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

RBC count

A

4.5-5.9 million/mm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

WBC count

A

(does not distinguish
subtypes which are estimated based on smears & dyes)
45,000-11,000/mm3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Erythropoiesis

A

Uncommitted stem cells go through a series of stages in the
bone marrow

  • Once the nucleus is expressed, leading to the formation of the reticulocyte, the cell is released into circulation where it becomes a mature RBC (erythrocyte)
  • Once the nucleus is expelled, the reticulocyte moves into circulation & becomes a RBC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Erythropoiesis stages

A

MEP (Megakaryocyte Erythroid Progenitor)

Proerythroblast

Early erythroblast

Intermediate Erythroblast

Late Erythroblast

Nuclear extrusion

Reticulocyte

RBC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Erythrocytes

A

Red Blood Cells
- Cytoskeleton creates
unique, concave shape

  • Flexible – swell in
    hypotonic medium, shrink
    in hypertonic medium
  • Some illnesses can affect
    RBC shape e.g. Sickle Cell
    Anemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Erythrocytes & Hemoglobin

A

Function to aid in O2 delivery to tissues
* Most O2 found in blood is bound to Hb in RBCs
* Hb gives blood its red colour
* RBC made up of 4 globin proteins (2 alpha, 2 beta), each with a heme group binding an iron molecule
* Heme iron combines with oxygen in the lungs & releases oxygen into
tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How many oxygen molecules can an RBC carry

A

Each RBC can carry over a billion molecules of oxygen (280 million Hb molecules/RBC x 4 heme groups)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Total arterial O2 carrying capacity in blood calculation

A

= O2 bound to Hb + unbound O2
= 197 mL HbO2/L blood + 3 mL dissolved O2/L blood
= 200 mL O2/L blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

WHat does oxygen saturation of blood depend on ?

A

LOCATION!

From a volume perspective:
* Blood entering tissues
contains 200 mL O2/L blood
* Blood leaving tissues contains 155 mL O2/L blood
* I.e. 45 mL O2 unloaded to the tissues

From a percentage perspective:
* In systemic arteries, ~97% of hemoglobin saturated with oxygen (oxyhemoglobin)
* Blood leaving in systemic veins
has an oxygen-hemoglobin
saturation of ~75%
* I.e. ~22% of the oxygen is
unloaded to tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Physiologic factors that change HB conformation

A

may affect O2 binding

Can be good e.g. help skeletal muscles receive more oxygen when
active compared to at rest (exercising muscle = ↓pH & ↑ temperature)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does a decrease in pH affect Hb affinity for O2

A

Decrease in pH decreases Hb affinity for O2 i.e. more offloaded into
tissues (opposite for increase in pH)

  • Muscle fibers produce lactic acid
  • Bohr effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How does an increase in temperature affect Hb affinity for O2?
Increase in temperature decreases Hb affinity for O2 i.e. more offloaded into tissues (opposite for decrease in temperature) * Higher temperatures weaken bond between O2 & Hb
26
Draw the Oxygen hemoglobin dissociation curve
A. Arterial blood saturation B. Oxyhemoglobin decreases by ~22% as the blood passes through the tissues from arteries to veins C. Oxygen reserve * Oxyhemoglobin remaining in venous blood * Enough to sustain brain & heart for ~4-5 minutes without breathing or CPR * Can also be used when tissue requirements increase e.g. exercise
27
2, 3 - Diphosphoglyceric Acid (2,3 - DPG)
Mature RBC lack nuclei, mitochondria and ER No protein/enzyme synthesis, or ability to repair membrane * Cannot respire aerobically i.e. the cells that carry O2 cannot use it * RBCs must obtain energy through anaerobic metabolism of glucose * At a certain point in the glycolytic pathway, a side reaction occurs that results in the production of 2,3-DPG * Enzyme that produces 2,3-DPG is inhibited by oxyhemoglobin i.e. when oxyhemoglobin levels decrease (e.g. hypoxia, anemia), 2,3- DPG production is increased * Increased 2,3-DPG concentration increases O2 unloading (shifts curve right)
28
which enzyme is inhibited by oxyhemoglobin
enzyme that produces 2,3-DPG i.e. when oxyhemoglobin levels decrease (e.g. hypoxia, anemia), 2,3- DPG production is increased * Increased 2,3-DPG concentration increases O2 unloading (shifts curve right)
29
what does increased 2,3-DPG concentration do?
increases O2 unloading (shifts curve right)
30
RBC lifecycle
- RBC's take 7 days to develop RBCs age and become fragile Lifespan of 120 days bilirubin produced when old RBCs are destroyed in the spleen
31
when is bilirubin produced
when old RBCs are destroyed in the spleen - breakdown product of heme from Hb - liver enzymes bind bilirubin and it is excreted into bile - phototherapy can also aid in breakdown - circulates in bile, some lost in urine/feces
32
Jaundice
associated with high blood concentrations of bilirubin from death of RBC (hyperbilirubinemia) skin and whites of eyes have yellow cast healthy newborns - rapid decrease in blood Hb at birth Preemies - inadequate amounts of liver enzymes needed to bind bilirubin so that it can be excreted in the bile (toxic) Phototherapy with blue light
33
Thalassemia
- Inherited defect in Hb, predominant among Mediterranean ancestry - alpha thalassemia: decreased synthesis of alpha Hb chains - Beta thalassemia: impaired synthesis of beta Hb chains - results in excessive destruction of RBCs - Leads to stillbirth, anemia, growth abnormalities, iron overload (leads to heart failure in young adults)
34
Sickle cell anemia
Inherited, recessive disease (2 copies of gene that produces Hb-S instead of Hb-A) Single amino acid substitute in the beta globin chain When deoxygenated, Hb-S polymerizes into long fibers (giving RBC sickle shape), which promote hemolysis Chronic, many clinical complications Lifelong (45 yr life expectancy) heterozygous environmental advantage - high resistance to malaria because plasmodium parasite (carried by mosquitos) cannot live in heterozygous RBCs
35
Plasma
straw coloured liquid 92% water ~1% dissolved solutes, trace elements (vitamins), & gases (CO2, O2) ~7% organic molecules * Amino acids * Glucose * Lipids * Nitrogenous waste * Proteins (most produced in liver)
36
Proteins found in blood plasma
1. albumins 2. globulins 3. fibronogen
37
Albumins
- produced in liver - provide osmotic pressure needed to draw water from surrounding tissue fluid into capillaries (maintain blood volume and pressure) - account for most of plasma proteins - albumins along with 9 other proteins account for 90% of plasma proteins (issue for new technology and drug discovery eg. mass spec only detects most abundant proteins) a protein found in blood plasma
38
Globulins
- Alpha & beta globulins produced in the liver & function to transport lipids & fat-soluble vitamins * Gamma globulins are antibodies produced by lymphocytes that function in immunity a protein found in blood plasma
39
Fibrinogen
- produced in the liver - important for clot formation a protein found in blood plasma
40
Blood Typing - how do we determine blood type?
Agglutination (clumping of RBCs) * Occurs when A-type RBCs are mixed with anti-A-type antibodies * Occurs when B-type RBCs are mixed with anti-B-type antibodies
41
agglutination
clumping of RBCs - occurs when A-type RBCs are mixed with anti-A-type antibodies - Occurs when B-type RBCs are mixed with anti-B-type antibodies how we determine blood type
42
Rh Factor
Another group of antigens found on RBCs * Rh positive more common than Rh negative * A/B antibodies cannot cross placenta but Rh antibodies can * May cause issues during birth if Rh- mother has an Rh+ positive baby (not an issue during pregnancy when fetal & maternal blood separate) * At birth mother may become sensitized & start to produce antibodies against Rh antigen * During next pregnancy, antibodies can cross placenta & cause RBC hemolysis in fetus (results in Hemolytic Disease in newborn) * Treatment: IV Rh immune globulin (RhIG) after birth of Rh+ baby to destroy fetal cells left in circulation before they elicit immune response
43
Blood clotting and 3 steps of it
Breaking endothelial lining of vessel exposes collagen proteins from subendothelial connective tissue to blood 3 steps initiated: 1. Vasoconstriction 2. Formation of platelet plug 3. Production of a web of fibrin proteins that penetrate & surround platelet plug
44
Blood clot formation
Clot formation: fibringen is converted by thrombin to fibrin * Via extrinsic pathway in vivo * Via intrinsic pathway in vitro
45
blood clotting process
Extrinsic pathway initiated by tissue factor (membrane glycoprotein found in walls of blood vessels & cells of surrounding tissue) * Blood vessel injury results in tissue factor becoming exposed to factor VII & others in the blood, creating a complex * This complex acts as an enzyme to activate factor X * Pathway then generates thrombin which can generate fibrin (important for clotting) from fibrinogen
46
Clot dissolution
plasminogen converted to plasmin which digests fibrin (promotes clot dissolution)
47
Myocardial Infarction
Heart attack patients usually treated initially with chewable aspirin to stop platelet clumping (before being evaluated for treatment with angioplasty or clot-dissolving drugs) * One of the most commonly used clot-dissolving medications in US ER departments are TPAs (tissue plasminogen activators) * Also applicable for stroke, blood clots, etc.
48
STEMI
ST Elevated Myocardial Infarction Most severe type of heart attack * Artery supplying blood to the heart becomes blocked * Fibrinolytic drugs are the preferred pharmacological class for STEMI treatment because they can achieve reperfusion unlike drugs from other classes * Fibrinolytics act by converting plasminogen to plasmin which in turn cleaves fibrin (results in clot dissolution & restoration of blood flow to ischemic tissues)
49
How do we treat heart attacks?
Fibrinolytic drugs are the preferred pharmacological class for STEMI treatment because they can achieve reperfusion unlike drugs from other classes Fibrinolytics act by converting plasminogen to plasmin which in turn cleaves fibrin (results in clot dissolution & restoration of blood flow to ischemic tissues)
50
Innate immune system
natural, not learned through experience includes 1st and 2nd line of defense it's non-specific
51
1st line of defense
part of the innate immune system includes physical and chemical surface barriers
52
2nd line of defense
internal cellular and chemical defense (if pathogen penetrates barriers) part of innate immune system non-specific
53
adaptive immune system
specific defenses 3rd line of defense - immune response (if pathogen survives specific, internal defenses)
54
leukopoiesis
uncommited stem cells in bone marrow give rise to progenitor cells for the remaining blood cells and platelets
55
platelets
develop to the megakaryocyte stage in the bone marrow and are released as platelets in circulation
56
neutrophils, monocytes and basophils
progenitor cells give rise to these cells which are found in circulation
57
lymphocytes
derived from their own lineage of lymphocyte stem cells in the bone marrow, which give rise to lymphocytes in the circulation leukocytes are able to move, squeeze through pores to get to sites - give rise to progenitor cells
58
Leukocytes
fancy name for WBCs includes: Granulocytes and Agranulocytes
59
Granulocytes
Type of leukocyte w lobed nucleus and granular appearance includes: Neutrophils Eosinophils Basophils
60
Agranulocytes
Type of leukocyte includes: lymphocytes, monocytes and macrophages
61
Basophils and mast cells
are granulocytes - cells named after morphology and how they stain morphology: lobed nucleus stain: cytoplasmic granules stain blue in hematoxylin dye function in inflammatory reactions and allergies release anticoagulant heparin (slows blood clotting) release histamine (vasodilator increasing blood flow to tissues) basophils found in circulation in low numbers make up <1% of WBC most cells are similar to basophils but are found in the tissues
62
Neutrophils
type of granulocyte morphology: segmented nucleus w 2-5 lobes stain: pink abundance: most abundant leukocyte (make up 54% - 62% of WBCs) function: immunity - early first responder to infections - phagocytose (ingest and kill) 5-20 bacteria during their short (1-2 day) lifespan
63
Neutrophil extravasation
1. Roll along the endothelial wall 2. are tethered, captured and activated 3. crawl to exit sites (endothelial cell junctions) 4. exit sites open due to signals btw leukocytes and endothelial cells
64
eosinophils
65
Eusinophils
Granulocytes Have a bilobed nucleus and stain bright red They Make up 1.3% of white blood cells Function= Defence against parasites Are Are in the G.I. tract urinary and genital epithelia, and they attached to large antibody coded, parasites, and released substances from granules to damage or kill
66
Schistrosoma
Second Most devastating, parasitic disease after malaria
67
Monocytes and macrophages
Are Agranulocyte they are 2 to 3 times larger than red blood cells and make up 3 to 9% of white blood cells Function = phagocytic Monocytes are the precursors for macrophages monocytes are found in the bloodstream, whereas macrophages are found in the tissues, both our primary tissue scavengers that are larger and more effective than neutrophils they in just 100 bacteria per lifetime and remove debris
68
Compare and contrast, monocytes and macrophages
Monocytes Are the precursors for macrophages and monocytes are found in the bloodstream, whereas macrophages are found in the tissues they are both primary tissue scavengers that are larger and more effective than neutrophils
69
How many bacteria do macrophages in just per lifetime
100
70
Tissue macrophages were originally called…
reticuloendothelial system And we’re Not associated with white blood cells when first described in different tissues, they acquired different names Microglia And histiocytes for the brain kupfer cells for the liver Osteo clasts for the bone and reticuloendothelial cells for the spleen
71
Monocyte Lifetime
Monocytes make up 3 to 9% of leucocytes in the blood, but only stay there for eight hours before they become macrophages monocytes in large and differentiate into macrophages during their eight hour commute from the blood to the tissue
72
Lymphocytes
Agranulocytes Only Slightly larger than red blood cells so they’re pretty small they make up 25 to 33% of white blood cells 5% are circulating while the rest are in tissues envountering countering pathogens. The adult body has 1 trillion lymphocytes their function is an immune response they include natural killer cells T lymphocytes also called T cells and B lymphocytes also called B cells
73
How many lymphocytes are there in the human body?
Approximately 1 trillion
74
What Proportion of white blood cells do lymphocytes make up
25-33% 5% Are circulating in the blood while the rest are in tissues in countering pathogens, they include natural killer cells, T cells and B cells
75
NK cells
Natural killer cells Type of lumphocyte Part of the second line of defense, they protect against viral infections, and some cancers. They can respond very quickly compared to other lymphocytes.
76
Mechanism of action of natural killer cells
1. Destroy target cells (infected or cancerous but not pathogen) by cell to cell contact 2. Can release interference and other cytokines uninfected cells 3. Can release IFNs and other cytokines to enhance the immune response, mediated by other cell types
77
Antigens And MHC markers
Antigen: A molecule often on the surface of a pathogen that the immune system recognizes as a specific threat MHC marker; Main tag on every single cell proteins, expressed on the surface of a cell display, both self and non-self antigens they are used primarily in the recognition of pathogens in the immune responses, but also used in self recognition includes MHC1 and MHCII
78
MHC1
An MHC marker found on the cell surface of all nucleated cells in the bodies of vertebrates
79
MHCII
Found Mostly on macrophages, B cells and dendritic cells also called a APCs
80
T cells
Lymphocytes Have receptors that antigens can be presented to buy antigen presenting cells APCs in order to activate T cells if a helper, T cell, CD4 encounters an APC with a foreign antigen fragment on the MHC II, the T-cell response by secreting cytokines to enhance the immune response not every helper, T cell will bind only ones that recognize specific antigens in a lock and key mechanism. Initial priming of lymphocytes to the antigen occurs in a lymph tissue.
81
Lymph tissue
Spleen, lymph nodes, tonsils and gut
82
T cell response
1. Threat an invader enters the body and first line of defense isn't enough 2. Detection - a macrophage encounters, engulfs and digests the invader - the macrophage places a piece of the invader (antigen) on its surface with the self (MHC) marker 3. Alert - the macrophage presents the antigen to a helper T cell and secretes a chemical that activates helper T cell - complex set of signals to activate helper T cell (recognition and verification to ensure its responding to non-self) - helper T cell divides and transforms into effector helper T cell 4. Alarm Effector helper T cell activates: A - cell mediated (T cell) response - naive cytotoxic T cell activated B - antibody-mediated/humoral (B cell) response - naive B cell activated
83
What are the general steps of immune response to foreign invader
1. Threat 2. Detection 3. Alert 4. Alarm (activation of T or B) 5. Building specific defences 6. Defence
84
Cell-mediated T-cell response
(this is after the alarm step, when an effector helper T cell has just activated naive cytotoxic T cells) 5. Building specific defenses - naive cytocoxic T cell divides into effector cytotoxic T cells and memory cytotoxic T cell 6. Defense - Effector cytotoxic T (CD8) cells targets cells displaying foreign antigen (tissue cells infected with intracellular pathogen) - Binds to MHC-I and kills infected cells by chemical means (perforin forms pores in target cell - gransymes enter pores - target cell apoptosis) 7. Memory T Cells stored for continued surveillance
85
Antibody-mediated (B-cell) response
(this is after the alarm step, when an effector helper T cell has just activated naive B cells) 5. Building specific defenses - Naive B cell divides into effector B cell and memory cell 6. Defense - Plasma cell (effector B cell) secretes antibodies which neutralize foreign proteins (toxins), trigger release of more complement, and attract more macrophages - antibodies target pathogens or toxins outside of cells by binding to the specific antigen(s) that initiate prior events 7. Continued surveillance - memory B cells stored for continued surveillance - when re-exposed to appropriate antigen, rapidly expand and produce more effector plasma cells and memory cells
86
Clonal Selection Theory
many B cells at birth but almost all of them are different B lymphocytes inherit ability to produce particular antibodies --> any given B cell can produce only one type of antibody but they are naive exposure to antigen stimulates B cell to divide many times until large population of genetically identical B cell clones are produced B cells are able to produce close to 2000 antibodies per second
87
How is the encounter of a pathogen remembered
The encounter is remembered in the form of memory cells Primary response: - first exposure to antigen - slower and weaker response - produces mostly IgM antibodies Secondary response: - Lymphocytes clone and memory cells result in faster and stronger response - produces IgG antibodies
88
Primary vs secondary response to antigen
Primary response: - first exposure to antigen - slower and weaker response - produces mostly IgM antibodies Secondary response: the thing is remembered! clones are there as warriers to attack - Lymphocytes clone and memory cells result in faster and stronger response - produces IgG antibodies
89
Antibodies
they target pathogenic bacteria - don't destroy them, just mark them as targets for immunological attack - pathogen may be attacked by innate immune cells (macrophages and neutrophils) - pathogen may be attacked by complement (blood protein defense system)
90
The complement pathway
9 complement proteins (C1-C9) that are inactive in the plasma Proteins become activated when antibodies mark the antigens There are 3 pathways which all lead to same outcome 1. Classical pathway (high level activity triggered by antibody) 2. Alternative pathway (low level, continuous activity) 3. Lectin pathway - similar to classical a type of innate, humoral immunity (always ready to go and found in blood) a type of adaptive, humoral immunity (can be specialized to a pathogen) made up of small, mostly inactive proteins in the blood
91
what are the 3 complement pathways
1. Classical pathway 2. Alternative pathway 3. Lectin pathway
92
What happens when the complement pathway is trigered
The complement pathway is made up of small, mostly inactive proteins in the blood When triggered, proteases cleave specific proteins and initiate an amplifying cascade followed by additional cleavages End result: 1. massive amplification of response 2. formation of cell-killing membrane attack complex (MAC)
93
MAC
Membrane attack complex kills cells 1. Recognition C1 2. Activation C4 C2 C3 (in this order) 3. Attack C5 C6 C7 C8 C9
94
Classical pathway
a pathway of the complement pathway starts with antibodies and CI proteins binding to the surface of pathogen
95
Lectin pathway
starts with lectins binding to mannose residues on the surface of the pathogen Lectins are carbohydrate-binding proteins that are highly specific for sugar moieties
96
Lectins
are carbohydrate-binding proteins that are highly specific for sugar moieties used in lectin pathway of the complement pathway
97
Complement cascade write it out
1. Activation of C1 (classical pathway) 2. C1 catalyses hydrolysis of C4 into C4a and C4b 3. C4b binds plasma membrane and is active 4. C3 cleaved into C3a and C3b - due to intermediate step involving splitting of C2 - alternative pathway also results in cleavage of C3 through a different sequence of events (pathways converge at transport?) 5. C3b converts C5 into C5a and C5b 6. C3a and C5a stimulate mast cells to release histamine - also serve as chemokines (attract macrophages, neutrophils, monocytes and eosinophils) 7. C5, C6, C7, C8 and C9 inserted into bacterial cell membrane to form a MAC = membrane attack complex
98
MAC
membrane attack complex - large pore that kills bacterial cell through osmotic influx of water - formed by C9 units
99
Inflammation
a defensive process Blood vessels widen 1. Redness - blood flow carries defensive cells and chemicals to damaged tissue, removing toxins 2. Heat - increases the metabolic rate of cells in the injured area to speed healing Capillaries become more permeable 3. Swelling - fluid containing defensive chemicals, blood-clotting factors, oxygen, nutrients and defensive cells seeps into injured area 4. Pain - hampers movement, allowing the injured area to heal
100
RICE
Rest Ice Compression Elevation - how we treat inflammation
101
When does inflammation occur?
in response to tissue damage and stress bruises and torn tissue (acute inflammation) disease states such as arthritis, obesity, etc. (chronic inflammation)
102
Sepsis
whole body inflammation that causes organ dysfunction (potentially fatal) symptoms: high fever, rapid pulse / respiratory rate, hypotension, hypoxemia, oliguria acidosis treatment: antibiotics, IV fluids septic shock: blood pressure falls so low that organs are not adequately perfused
103
Endotoxin and sepsis
- Bacteria lipopolysaccharide (component of gram-negative bacteria) that is usually the cause of sepsis - Localized infection: triggers innate immunity - when large amounts enter circulation, inflammatory cytokines are released
104
Fever
defensive process - infection leads to fever - teething also results in fever - exogenous pyrogens cause the release of IL1 and FN which signal to receptors in hypothalamus to decrease heat loss and increase heat production resulting in increased temp = fever
105
autoimmunity
immune system functions by distinguishing "self" from "non-self"
106
autoimmune diseases
a failure of immune system to recognize and tolerate self-antigens there are over 40 autoimmune diseases, affecting 5-7% of the population
107
Reasons why self-tolerance may fail
( in relation to autoimmune diseases) 1. an antigen that does not normally circulate in the blood may become exposed to the immune system 2. A self-antigen that is otherwise tolerated may be altered by combining with a foreign haplen 3. Antibodies may be produced that are directed against other antibodies 4. Antibodies produced against foreign antigens may cross-react with self-antigens 5. Self-antigens may be presented to helper T cells together with MHCII 6. Autoimmune diseases may result when there is inadequate activity of regulatory (suppressor) T lymphocytes
108
AIDS
acquired immune deficiency syndrome caused by human immunodeficiency virus HIV - infects and destroys helper T cells in the gastrointestinal mucosa decreased immunological function and greater suceptibility to opportunistic infections and cancer
109
HIV
retrovirus that causes AIDS genetic code carried in RNA reverse transcriptase transcribes viral RNA into complementary DNA for viral replication
110
ART
antiretroviral therapy inhibits reverse transcriptase, suppressing HIV replication indefinitely ART is not a cure! - HIV viral DNA integrates itself into host DNA of memory helper T cells - when ART drugs not stopped, virus reappears - not all individuals with AIDS have access to ART drugs
111
Allergies
2 different pathways 1. Abnormal responses by B cells 2. Abnormal responses by T cells
112
Abnormal responses by B cells
One of the pathways of allergies - hay fever, asthma and most other allergies caused by IgE immediate hypersensitivity - Not allergic: allergen stimulate Th1 cells to secrete IFNg and IL2 Allergic: allergen stimulates Th2 cells to secrete IL4 and IL13 which stimulate plasma cells to secrete IgE antibodies instead of IgG Plasma cells bind to mast cells and basophils, stimulating them to release hestamine and other cytokines (produces immune reaction ie. trouble breathing, itching, sneezing)
113
Abnormal response by T cells
delayed hypersensitivity - hours to days because the reaction is mediated by lymphokines instead of antibodies ex. contact dermatitis due to poison ivy - get hives hours to days late
114
ADH
(antidiuretic hormone) /vasopressin synthesized in the hypothalamus & stored in posterior pituitary increases water retention/reabsorption by kidneys creates more water in blood (decreased osmolality) and less water / more concentrated urine
115
Dehydration
is increased plasma osmolality - increased release of ADH by posterior pituitary - - stimulates more resorption from the kidneys in order to increase the water in the blood, concentrate/decrease water loss from urine and decrease blood osmolality via this negative feedback response
116
Over-hydration
when there;s low plasma osmolality - stimulates decrease in water reabsorption in the kidneys (creates less water in blood, more in urine - dilute pee)
117
Brattleboro rats
Mutation in ADH gene resulting in no ADH production (so no retention of water by kidneys and very high plasma osmolality) * Excessive thirst * Excess dilute urine * Diabetes insipidus (kidneys cannot conserve water)
118
ADH and nocturnal urination
Generally, ADH follows a circadian rhythm in children i.e. ADH levels increase at night * Increased absorption of water * Decreased production of urine
119
Body water content by biological sex and age
* Babies – 75% * Women – 50% * Men – 60% * Elderly men & women – 45%
120
Body water content - how much is intracellular vs. extracellular
2/3 intracellular 1/3 extracellular
121
Water intake split
- Drinking fluid & water in food (2250 mL) * Water produced by metabolism (250 mL) 2500mL total
122
Water loss split
- Urine (1500 mL) * Feces (100 mL) * Sweat (200 mL) * Lungs (700 mL)
123
Rule of 3
A human can survive for 3 minutes without air * In a harsh environment, a human can survive for 3 hours without shelter * A human can survive for 3 days without water * A human can survive for 3 weeks without food
124
Exceptions to rule of 3
Iran, 2004 * A 97 year old woman survived for 8 days without food or water, under the rubble of her home, after an earthquake Mexico City, 1985 * Newborn babies trapped in wreckage of hospital after an earthquake, rescued 4-7 days later & nearly all survived * Known as the “Miracle Babies”
125
Unique animals and water regulaiton
Dessert mammals: * Arabian camel * Desert rodents * Antelopes Marine mammals Hibernating mammals
126
The Arabian Camel
- Survive without water in desert for several days in hot & dry environment * May be active under these conditions * Cannot halt the function of their kidneys * Lipid stored in hump * Lipid metabolism provides a significant amount of metabolic water * Dry food provides some water (even dry hay) * Kidneys efficient at water recovery - Primarily used for racing
127
Arabian camel when hydrated
Thermoregulate by panting * Core body temperature = 36.5-38.5°C
128
Arabian camel when dehydrated
- No panting * Core body temperature = 34.5-40.5 °C Turn off thermoregulation for water conservation * Supercooling at night * Overheating during day
129
The Kangaroo Rat
- Small, arid desert-adapted species * High oxygen consumption & respiratory water loss * Survive without drinking water (even when available) * Maintain body temperature * Obtain water from dry food & metabolism * Live in colonies underground – moist air in burrows reduces respiratory water loss * Nocturnal (avoid heat of day) * Produce very dry feces
130
what is the percent of dissolved salts in fresh vs. sea water vs. human body
Fresh water = 0.1% dissolved salts Human body = 0.9% dissolved salts Sea water = 3.5% dissolved salts When humans drink salt water, we become dehydrated
131
How do marine mammals get water
Marine mammals have no access to fresh water Only salt water (3.5% dissolved salts) * Obtain water from food (krill, fish, plankton) & metabolism * Produce very concentrated urine
132
Hibernating bears - how do they survive
Grizzly bears hibernate for half of the year & live completely off of stored fat reserves * Burn up to 8000 calories/day * Do not eat, defecate, drink, or urinate * Reduce their metabolic rate & heart rate * Metabolic water from lipids balance respiratory water loss * Urea recycled to produce protein * Water reabsorbed from bladder
133
Kidneys
Essential organs for life * Excrete metabolic waste products * Involved in other homeostatic processes * Water & electrolyte regulation * Acid-base (pH) balance * Major blood vessels associated (renal artery & vein)
134
What homeostatic processes are the kidneys involved in?
- Water & electrolyte regulation * Acid-base (pH) balance
135
________ drain urine from kidneys by ____________
ureters drain urine from kidneys by peristalsis urinary bladder for urine storage urethra drains bladder
136
What drains the bladder?
URETHRA!
137
Kidneys structure
- Renal cortex * Renal medulla * Major arteries & veins * Papillae of the renal medulla (renal pyramids) * Renal pelvis connected to ureter
138
How do kidneys differ for horses, cows and dogs?
Horses = triangular shape Cows - lumpy Dog = kidney bean shape
139
What is the nephron?
Functional unit of the kidney * Blind-ended microscopic tubules * Each human kidney contains >1 million nephrons * Nephrons are lost with age & cannot be replaced * All regions associated with networks of peritubular capillary vessels
140
How many nephrons are there per kidney?
Each human kidney contains >1 million nephrons - 80% of nephrons are cortical * 20% of nephrons are juxtamedullary (i.e. dip into the medulla)
141
Blood path through the nephron (broad_
1. Blood enters the glomerulus 2. Blood is filtered through the nephron 3. Urine exits out the collecting duct
142
4 regions of the nephron
1. Bowman’s/glomerular capsule (contains glomerulus) 2. Proximal convoluted tubule 3. Loop of Henle 4. Distal convoluted tubule
143
Are collecting ducts part of the nephron
Collecting ducts play an essential role in water retention but are not normally considered to be part of the nephron
144
How much fluid enters bowman's capsule per day and how much is excreted as urine?
180L fluid/day enters Bowman’s capsule * 1.5L fluid/day is excreted as urine
145
What are the 3 parts of urine formation
1. Filtration 2. Reabsorption 3. Secretion
146
Filtration
- First part of urine formation - Movement of fluid from blood to lumen of nephron * Only takes place in “renal corpuscle” where glomeruli & Bowman’s capsule allow for bulk flow of fluid Blood hydrostatic pressure forces blood plasma out of the glomerulus into Bowman’s capsule Inner layer of Bowman’s capsule made up of podocytes * Intricate interdigitation of pedicels * Filtration slits/diaphragms * Act as filters * Negatively charged * Major barrier to proteins (plasma protein = 7%, glomerular filtrate protein = 0.03%) * Mutations in slit proteins results in proteinuria (protein in urine) * Smaller plasma solutes easily enter glomerular filtrate
147
Where does filtration occur?
Only takes place in “renal corpuscle” where glomeruli & Bowman’s capsule allow for bulk flow of fluid filtration slits between podocytes of Bowman's capsule act as filters
148
Bowman's capsule structure
It's the primary filter for urine formation Inner layer of Bowman’s capsule made up of podocytes * Intricate interdigitation of pedicels * Filtration slits/diaphragms
149
filtration slits/diaphragms
btw podocytes of bowman's capsule Act as filters * Negatively charged * Major barrier to proteins (plasma protein = 7%, glomerular filtrate protein = 0.03%) * Mutations in slit proteins results in proteinuria (protein in urine) * Smaller plasma solutes easily enter glomerular filtrate
150
Daily glomerular filtrate production
= ~180L/day in healthy men & ~150L/day in healthy women * Equivalent to the entire blood volume being filtered every 40 mins * Most of this is recovered since daily urine volume = ~1.5L/day
151
Glomerular filtration rate (GFR)
Determined by glomerular blood hydrostatic pressure in the glomerular capillaries lood hydrostatic pressure can change (e.g. with exercise), but GFR is relatively constant at 125mL/min (both kidneys) Relatively stable GFR ensures constant flow of glomerular filtrate, allowing reabsorption to occur & waste to be eliminated
152
GFR and increased blood pressure
↑ blood pressure → afferent arteriole constricts & efferent arteriole dilates
153
GFR and decreased blood pressure
↓ blood pressure → afferent arteriole dilates & efferent arteriole constricts
154
Juxtaglomerular apparatus includes:
(This is for filtration) Juxtaglomerular cells Macula densa cells Mesangial cells Sympathetic nerve fibres
155
Juxtaglomerular cells:
part of juxtaglomerular apparatus involved in filtration smooth muscle cells in the afferent arteriole
156
Macula densa cells
part of juxtaglomerular apparatus sensory cells in a region of the distal convoluted tubule
157
mesangial cells
part of juxtaglomerular apparatus involved in filtration connect juxtaglomerular and macula densa cells i.e. communication
158
Sympathetic nerve fibres
associated with afferent arterioles; redirect blood from kidney to other organ systems involved in filtration part of Juxtaglomerular Apparatus
159
RAAS steps
Renin-Angiotensin System 1. Blood pressure falls 2. Juxtaglomerular cells secrete renin into the blood 3. Renin acts on angiotensinogen to produce angiotensin I (ANGI) 4. ANGI is converted into ANGII by angiotensin converting enzyme (ACE) 5. ANGII is a vasoconstrictor 6. Blood pressure increases (draw it out!!)
160
Angiotensin II
Stimulates aldosterone secretion from adrenal cortex * Acts with aldosterone to increase salt & water retention by kidneys (increases blood volume)
161
Blood flows from the glomerulus into the _________ ____________
- Blood flows from the glomerulus into the peritubular capillaries * Blood vessels, after going through the glomerulus, continue winding around the nephron * Blood vessels send more water/solutes into the nephron as needed * Blood vessels draw water/solutes out of the nephron as needed
162
Reabsorption
second step of filtration After filtrate leaves Bowman’s capsule, it is modified by reabsorption * Substances in the nephron tubules flow back into blood Excess K+ from glomerular filtrate returned/reabsorbed into peritubular capillaries (blood) in proximal convoluted tubule * ~65% of salt & water in original glomerular ultrafiltrate reabsorbed across proximal tubule & returned to vascular system * ~20% returned to vascular system by reabsorption through descending limb of loop of Henle
163
X% of salt & water in original glomerular ultrafiltrate reabsorbed across proximal tubule & returned to vascular system
65
164
X% returned to vascular system by reabsorption through descending limb of loop of Henle
20
165
Peritubular capillaries
During reabsorption Excess K+ from glomerular filtrate returned/reabsorbed into peritubular capillaries (blood) in proximal convoluted tubule Tight junctions of the proximal convoluted tubule cells are leaky → paracellular transport Transportation can also occur through the cell → transcellular transport
166
Secretion (urine formation)
Last step of urine formation Opposite of reabsorption * Active transport of substances from the peritubular capillaries into the tubular fluid
167
Osmolality based on region
Glomerulus = 300 Os Proximal tubule = 300 Os bottom of loop of Henle = 1200 Os Top of loop of Henle = 200 Os Distal confoluted tubule = 100 - 300 then Top of collecting duct = 300 Bottom of collecting duct = 1200
168
Loop of Henle
Sets up hyperosmotic environment in renal medulla (juxtamedullary nephrons) so that urine concentration can occur Includes descending loop of henle and ascending loop of henle follws proximal tubule
169
Descending loop of Henle
* Thin-walled * Filtrate becomes very concentrated (from 300 to 1200 mosm/L as it reaches loop turn) * Allows water to be drawn out i.e. impermeable to salt & permeable to water
170
Ascending loop of Henle
* Thick-walled * Rich in mitochondria * Salt actively extruded & sent back into interstitial fluid i.e. permeable to salt & impermeable to water * Concentration (osmolality) decreases from 1200 back to 300 mosm/L
171
Countercurrent multiplier system
(of loop of Henle) 1. Descending limb is passively permeable to water, making the concentration in the tubule more concentrated 2. Extrusion of salt from ascending limb makes the surrounding interstitial fluid more concentrated 3. Deepest region in the medulla reaches a concentration of ~1200-1400 mosm/L
172
The Collecting Ducts
Several nephrons drain into each collecting duct * Under influence of ADH, water drawn out of filtrate by osmosis from medullary collecting duct into blood * I.e. ADH must be present to make urine hyperosmotic (more concentrated than blood)
173
What must be present in the collecting ducts to make urine hyperosmotic?
ADH! (hyperosmotic = more concentrated than blood)
174
The Collecting Ducts processsss (4 steps)
1. ADH/vasopressin (AVP in diagram) binds receptor 2. Signals cAMP 3. Inserts AQP2(aquaporins) on apical side 4. Water absorbed by osmosis (basolateral side) into blood
175
The Vasa Recta
Blood vessels associated with nephron loop (peritubular capillaries associated with cortex portion of nephron, vasa recta associated with medulla portion of nephron) Act as counter current exchange system (not the same as counter current multiplier) Diffusion of salt and water changes the salt concentration of the interstitial fluid in the renal medulla Therefor, maintains standing osmotic gradient
176
The Ureters
Urine moves from renal pelvis /kidney) to ureter * Smooth muscle in walls carry out peristalsis * Peristalsis waves move urine toward bladder * Backflow of urine from bladder prevented by flap valve
177
What prevents backflow of urine from bladder
a flap valve
178
Vesicoureteral reflux
When the one way valve btw ureter and bladder is not working right, backflow of urine into the kidneys may occur
179
Hyperosmotic Urine
= normal urine - Sterile * Pale to dark yellow * Rapidly populated by bacteria (source of ammonia odour) * pH range: 4.5-8.2
180
pH range of normal urine
4.5-8.2
181
Substances in urine that may indicate disease states
The following should not be found in the urine: - protein, - glucose -blood cells - hemoglobin - bile
182
Chronic Kidney Disease
CKD - the severity/stage of CKD is inversely proportional with the GFR ie. the higher the stage, the lower and least efficient the GFR is >10% of people (>20 million) aged 20+ in the US have CKD * More common among women * >35% of people aged 20+ with diabetes have CKD * >20% of people aged 20+ with hypertension have CKD
183
Proportion of people with kidney disease
>10% of people (>20 million) aged 20+ in the US have CKD * More common among women * >35% of people aged 20+ with diabetes have CKD * >20% of people aged 20+ with hypertension have CKD
184
What do we use to treat kidney failure?
DIALYSIS! includes: Blood removed for dialysis Arterial pressure monitor Blood pump Heparin pump (to prevent clotting) dialyzer inflow pressure monitor dialyzer (filter) venous pressure monitor air trap and air detector air detector clam filtered blood returned to body
185
Nephrolithiasis
= KIDNEY STONES! - Hard objects formed by the kidneys containing crystalized minerals/waste products (concentrations exceed solubility) * Increased incidence with dehydration * Large stones in calyces or pelvis may obstruct urine flow * Small stones (<5mm) pass into ureter and can cause severe pain * If medications do not cause stone to pass, individual may need - lithotripsy (shock waves to shatter stone) * Surgery may be required if lithotripsy is unsuccessful
186
Types of kidney stones
- Calcium stones – calcium phosphate/ calcium oxalate * Struvite stones – crystals of magnesium ammonium phosphate (may result from UTIs) * Uric acid stones – occur in individuals with gout * Cysteine stones – occur in individuals with cystinuria
187
Urinary Incontinence
Uncontrolled urination due to loss of bladder control includes: - STRESS urinary incontinence and - URGENCY incontinence
188
Stress urinary incontinence
urine leakage due to increased abdominal pressure (sneezing, laughing, coughing) * Occurs in females when pelvic floor no longer provides adequate support to urethra due to childbirth or aging * Occurs in males as a result of prostate cancer treatment
189
Urgency incontinence
uncontrolled contractions of detrusor muscle
190
How is urinary incontinence diagnosed
Diagnosis through urodynamic testing and cystometric tests (test bladder pressure and compliance)
191
Diabetes insipidus
Characterized by: * Polyuria (large urine volume from 3-10L/day) * Polydipsia (drinking a lot of fluids) * Urine is dilute (hypotonic concentration of <300mOsm) * 2 major types of diabetes insipidus: 1. Central diabetes insipidus 2. Nephrogenic diabetes insipidus
192
Polyuria
Characteristic of Diabetes insipidus - large urine volume from 3-10L/day
193
Polydipsia
Characteristic of diabetes insipidus means drinking a lot of fluids
194
hypotonic urine
means dilute urine concentration of <300mOsm
195
Central diabetes insipidus
- Inadequate secretion of ADH * Treated with Desmopressin (synthetic ADH)
196
Nephrogenic diabetes insipidus
- Inability of the kidneys to respond to ADH * Individuals must drink a lot of water to prevent dehydration
197
Hyperkalemia
Hyperkalemia: plasma K+ concentration >5mEq/L * Results in nausea, weakness, and EKG changes
198
Hypokalemia
Hypokalemia: plasma K+ concentration <3.5mEq/L * Results in heart arrhythmias and muscle weakness * Caused by some diuretics, vomiting, metabolic alkalosis, or excessive aldosterone secretion
199
What should plasma K+ concentrations usually be?
Plasma K+ concentration should normally be between 3.5-5mEq/L if below = hypokalemia if above = hyperkalemia
200
AMS
Acute Mountain Sickness Occurs when individuals move to high elevations without being adequately acclimatized (involves the respiratory and renal systems) * Respiratory system acclimates through hyperventilation * Kidneys will acclimate by undergoing diuresis, resulting in hypovolemia (decreased blood volume) which helps mitigate AMS symptoms * Done in response to decreased ADH and aldosterone secretion, and increased natriuretic hormone secretion
201
Treatment for acute mountain sickness
Acetazolamide (inhibits carbonic anhydrase) * Decreases renal absorption of bicarbonate (and water), producing mild diuretic effects and metabolic acidosis * Acidosis promotes hyperventilation which aids acclimatization