Remaining material Flashcards
1
Q
What happenned with medicine before the 17th century during 460-370 BC?
A
- Hippocrates postulated the “Humoral Theory” ie blood, phlegm, black bile and yellow bile
- Theory states that an imbalance in these factors causes disease eg yellow bile found in gall bladder and showed itself with jaundice
2
Q
What is medicine like from 129-216 AD?
A
- Galen connected humoral medicine with Greek natural philosophy
- Each humour had one or more qualities: hot, cold, dry, or wet
- Body and nature shared similar qualities (eg, heat, moisture)
- Human body (microcosm) was seen as a smaller version of the universe (macrocosm), and they influenced each other
- Thought that the body and nature worked the same way
3
Q
What is an example?
A
eg. combo of hot and wet
- Produces air element and blood humour
- Blood predominated in Spring
- Person with natural excess of blood had a sanguine physical and psychological humoural constitution or temperament
- A long time ago, people thought our bodies had 4 special liquids called humours. One of them was blood
- Blood was thought to be warm and wet
- They said it was connected to the air and springtime
- If someone had a lot of blood, they were called sanguine
- They meant they were usually happy, energetic, and friendly
So basically, people beleived your personality and health came from how much of each liquid (humour) you had inside you
4
Q
If unhealthy what is the key to restore balance?
A
- Lifestyle (diet and excericse)
- Medication (herbs)
5
Q
What does opposites cure oppites mean??
A
So if you had a hot sicknesses, they would give you something cold to make you feel better
- Illness seen as internal disorder of the body, not the result of a specific agent like bacteria; didnt known bacteria existed; thought sickness came from in your body, not from tiny bugs like we know today
6
Q
How long did the humoural vision of body last?
A
Until late 17th century in Europe; by middle ages seen as “quackery”
- New science of Galileo, Descartes, Newton & Boyle replaced Aristotelian, qualitative, natural philosophy with a mechanical, chemical, and mathematical vision of the world and body
7
Q
What happenned during the 1200-1500s?
A
Notion of pulmonary cicrulation
8
Q
What happenned during the 1600s?
A
Valves in veins; blood circulates body and is pumped by the heart
9
Q
What happenned during 1658?
A
First description of RBCs by a 21 year old microscopist
10
Q
What happenned during 1661?
A
Capillary system
11
Q
What happenned during 1665?
A
First recorded blood transfusion (dog to dog)
12
Q
What happenned during 1667?
A
First human blood transfusion (lamb to boy) most failed since blood types hadnt been discovered
13
Q
What happenned during 1674?
A
Anton van Leeuwenhoek discovered that RBC are 25,000 times smaller then a grain of sand
14
Q
What happenned during 1700-1800s?
A
Transfusions still failing
15
Q
What happenned during 1800s-1900s
A
Properties of blood emerge (coagulation factors, platelets in clots, etc)
- Successful human blood transplants
16
Q
What happenned during 1917?
A
- Red cross organized civilian blood donor service during WW1 and II leading to new developments in storing and using blood
- Optimized glucose-citrate solutions (prevent coagulation and allow for viable storage)
17
Q
What happenned during 1959?
A
X ray crystallography revelas hemoglobin structure (portein in RBCs that carry oxygen)
18
Q
What happenned during 1965?
A
Slowly thawing frozen plasms precipitated factor VIII (antihemophilic factor) which has great clotting power
- Adding this fscotr via replacement therazpy helps to stop and prevent bleeding
19
Q
What happenned during 1971?
A
Hep B discovered through infected donours
20
Q
What happenned during 1981?
A
First case of AIDS
- Hemophiliacs discovered AIDS suggesting a blood-borne component
21
Q
What happenned during 1983 and 1984?
A
- AIDS virus identified
- Patients infeced with blood borne pathogens from trasfusions led to screening and lawsuits
22
Q
What are the functions of the circulatory system?
A
- Transportation of all substance essential for cellular metabolism
- Respiratory (RBCs)
- Nutrition (digestive)
- Excretory (waste) - Regulation
- Hormonal
- Temperature - Protection
- From injury (clotting)
- From pathogens (immune)
23
Q
What is blood made of?
A
- Plasma (yellow liquid part)
- Carries water, proteins, nutrients, waste, and gases - Blood cells, which come in 3 main types:
- RBC: carry O2
- WBC: fight germs and keep you healthy
- Platelets: help you blood clot when you get a cut
24
Q
What is hematopoiesis?
A
- Formation of blood cells
- Hematopoietic stem cells orginate in the embryo and migrate to diff 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
25
What do the blood samples after centrifugation look like?
RBC:
- Most abundant blood cells
- Biconcave disk shape
- Packed at bottom
WBC, platelets:
- Thin, light interface
- "Buffy coat"
Plasma fluid sits at very top
26
What can distinguish subtypes of blood?
Blood smears and biological dyes can distnguish (can see diff parts of the RBC using dyes)
27
What is erythropoiesis?
- 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 nucelus is expelled, the reticulocyte moves into circulation and becomes a RBC
Simplified:
- Stem cells in bone marrow start process
- Grow and chance through diff steps
- One step is called a reticulocyte (an almost ready RBC)
- Nucelus (cell brain) gets pushed out
- Cell enters the blood and becomes a mature RBC
28
What is a RBC (erythrocyte)?
- Cytoskeleton creates unique, concave shape
- Flexible: swell in hypotonic medium; shrink in hypertonic medium
- Some illnesses can affect RBC shape eg sickle cell anemia
29
What does hemoglobin do?
- Functions to aid in O2 delivery to tissues
- Most O2 found in blood to Hb in RBCs
- Hb gives its red colour
- RBC made up of 4 global proteins (2 alpha, 2 beta), each with a heme group binding an iron molecule
- Heme iron combines with O2 in the lungs and releases oxygen into tissue
30
How much o2 can rbc carry?
each RBC can carry over a billion moecules of oxygen (280 million Hb molecules/RBCx 4 heme groups)
31
What is the total arterial O2 carrying capacity of the blood?
=O2 bound to Hb+ unbound O2
= 197 mL HbO2/L blood+ 3mL dissolved O2/L blood
= 200 mL O2/L blood
How much oxygen is in 1L of blood:
- 197 mL is carried by hemoglobin
- 3 mL is floating in blood
- 200 mL of oxygen per litre of blood
32
How does O2 saturation depend on location from a volume perspective?
Blood entering tissues contains 200 mL O2/L blood
- Blood leaving tissues contains 155 mL O2/L blood
- ie 45 mL O2 unloaded to the tissues
33
How does O2 saturation depend on location from percentage perspective?
- In systemic arteries, about 97% of hemoglobin saturated with oxygen (oxyhemoglobin)
- Blood leaving in systemic beins has an oxtgen hemoglobin saturation of about 75%
- ie 22% of the oxygen is unloaded to tissues
34
Can things like pH and temp change how hemoglobin (Hb) holds O2?
- Muscles get warmed and more acidic (lower pH)
- Makes hemoglobin let go of oxygen more easily, so your muscles get more O2
Key points:
- Low pH=hemoglobin holds O2 less tightly means O2 goes into tissues (called Bohr effect; muscles make acid during excercise)
- High temp=hemoglobin also holds oxygen less tighelty (heat weakens the bond between hemoglbin and O2)
35
What does the oxygen-hemoglobin dissociation curve look like?
A. arterial blood saturation
- your blood leaving the lungs is almost full of oxygen (close to 100% saturated)
B. ocygemoglobin drops about 22% in tissues; as blood moves through your body (frome arteries to veins), hemoglobin lets go of about 22% of its oxygen so tissues can use it
C.Oxygen reserve
- Still some O2 left in the blood after passing through tissues;
this leftover oxygen:
- can keep your brain and heart alive for 4-5 mins if you stop breathing
- Helps durig things like exercise, when tissues need more oxygen
Right shift= hemoglobin lets go of more O2 (good during excercise)
Left shift= hemoglobin holds on to oxygen more tightly (not great for active tissues)
36
What is 2,3-DPG? (2,3-Diphosphohlyceric Acid)?
- Mature RBC lack nuclei, mitochondria and ER
- No protein/enzyme synthesis, or ability to repair membrane
- Cannot repair aerobically ie the cells that carry O2 canot use it
- RBCs must obtain energy through anerobic metabolism of glucose
- At a certain point in the glycolytic pathway, a side reaction occurs thst results in the production of 2,3-DPG
- Enzyme that produces 2,3-DPG is inhibited bt oxyhermoglobin ie when oxyhemoglobin levels decrrase (eg hypoxia, anemia) 2,3-DPG production is increased
- Increased 2,3-DPG concentration increases O2 unloading (shifts curve right)
Helps red blood cells let go of O2
- when there is less o2 in the body (like anemia or low o2) the rbcs make more 2,3-DPG
- more 2,3-dpg means more o2 is released from hemoglobin into tissues
- called a right shift on the o2-hb curve
Right=release (oxygen goes to tissues)
Left=lock (hemoglobin holds onto O2)
37
What is the RBC lifecycle?
- Take 7 days to develop
- RBCs age and become fragile
- Lifespan of 120 days
- Bilirubin produced when old RBCs are destroyed in the spleen
- Breakdown product of heme from Hb
- Liver enzymes biind bilirubin and it is excreted into bile
- Phototherapy can also aid in breakdown
- Circulates in bile, some lost in urine/feces
(rbcs are broken down in spleen, heme part of hemoglobin is turned into a yellow waste called bilirunin, liver produces bilirubin and sends it out to bile, some bilirubin also leaves in pee and poop); phototherapy (light treatment) can help break down bilirubin too (often used in babies with jaundice)
38
What is jaundice?
- Assocaited with high blood concentrations of billirubin from death of RBC (hyperbilirubinemia)
- Skin and whites of eyes habe yellow cast
- Healthy newborns-rapid decrease in blood Hb at brith
- Preemies- inadequate amounts of liver enzymes needed to bind bilirubin so that it can be excreted in the bile (toxic)
- Phototherpay with blue light
39
What is thalassemia?
- Inherit 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)
40
What is 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 clinial complications
- Lifelong about 45 year life expectancy
- Hterozygous environmental advantage- high resistance to malaria because plasmodium parasite (carried by mosquitos) cannot live in heterozygous RBCs
41
What is used to test for sickle cell anemia?
Protein electrophoresis by looking at diff types of hemoglobin
How it works:
- Blood sample is placed in a gel and connected to a power source
- Electricity makes hemoglobin proteins move through the gel
- Diff types of hemoglobin move at diff speeds based on their charge
What results show:
1. Normal (HbA/HbA)
- only hemoglobin a present
2. Sickle cell anemia (HbS/HbS):
- only hemoglobin S is present
- doesnt mvoe as far
42
What is plasma made of?
about 92% water
about 1% dissolved solutes, trace elements (vitamins), and gases (CO2, O2)
- About 7% organic molecules
- Amino acids
- Glucose
- Lipids
- Nitrogenous waste
- Proteins (most produced in liver)
43
What proteins are found in blood plasma?
1. Albumins
- Made in liver
- Provide osmotic pressure needed to draw water from surrounding tissue fluid into capillaries (maintain blood volume and pressure)
- Account for most 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)
- made in liver; help pull water into blood vessles (keep blood volume and pressure normal), make up most of the plasma prtoeins
2. Globulins
- Alpha and beta globulins produced in the liver and function to transport lipids and fat soluble vitamins
- Gamma globulins are antibodies produced by lymphocytes that function in immunity
- Also made in liver; help move fats and vitamins through the blood, some (gamma globulins) are antibodies that help with immune defense
3. Fibrinogen
- Made in liver
- Important for clot formation
44
What are blood group antigens?
- Antigens are markers on red blood cells
- Antibodies are proteins in plasms that attack unfamiliar blood types
- O=universal donour (no antigens=no attack)
AB= universal reciever (no antibodies=accepts all)
O is most commonl AB is rarest
45
What is blood typing?
Agglunitination (clumping of RBCs)
- Occurs when A-type RBCs are mixed with anti-A type antibodies
- Occurs when B-type RBCs aremixed with anti-B type antibodies
(happens when wrong antibodies mix with wrong blood type)
- If you mix A-type blood with anti-A antibodies, the cells clump
- If you mix mix B-type blood with anti-B antibodies, cells clump
- Clumping=bad means immune system is attacking blood
46
What is a Rh factor?
another antigen (marker) found on RBCs, if you have it= rh positive (rh+), rh negative (rh-) most people are Rh+
- Usually not a problem; unless pregnancy is involved
- if an rh- mom is pregnat with rh+ baby; at birth some of the babys blood can mix with the moms; the body can start making rh antibodies (immune response)
- if shes pregant with another rh+ baby; her antibodies can cross the placenta and attack the babys red blood cells
- causes a serious problem called hemolytic disease of the newborn
How is it prevented:
- give the mom a shot of rh immune globulin (RhIG) after her first rh+ baby
- Destroys leftover fetal cells before her immune system reacts
47
What is blood clotting and the steps for them?
- Breaking endothelial lining of vessels 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 and surround platelet plug
48
What happens during clot formation?
Clot formation: fibrinogen is converted by thrombin to fibrin
- via extrinsic pathway in vivo (happens inside the body, like from a injury) injury from outside the body
- via intrinsic pathway in vitro (happens in lab tests or with damaged blood vessel walls)
49
What happens when there is a problem with clotting factors?
- Bleeding disorders (like hemophilia or vitamin K deficiency)
50
How does blood clotting happen via the extrinsic pathway?
- Pathway starts when you get an injury outside the blood vessel (like a cut)
Step by step (made easy):
1. Tissue factor (a special protein from damaged tissue) is exposed
2. It meets factor VII (clotting protein in blood)
3. Together they activate factor X
4. Factor X helps makes thrombin
5. Thrombin turns firinogen into fibrin (sticky threads)
6. Fibrin+ blood cells= a strong clot
51
What is the difference between coagulation and fibrinolysis?
Coagulation (clot forming):
- Thrombin turns fibrinogen (a protein in blood) into fibrin
- Fibrin forms sticky threads that create a blood clot
- This happens through the intrinsic and extrinsic pathways (as seen before)
Fibrinolysis (clot dissolving):
- Once healing starts, the body breaks down the clot
- A protein called plasminogen is turned into plasmin
- Plasmin cuts up the fibrin net the clot breaks apart
- Step helped by tPA (tissues plasminogen activator)
52
What happens in those who have myocaridal infarctions?
- Heart attack patients usually treated initially with aspirin to stop platelt clumping (before being evalutated for treatment with angioplasty or clot-dissolving drugs)
- One od the most clot-dissolving medications in US ER departments are TPAs (tissue plasminogen activators)
- Also applicable fr stroke, blood clots, etc
53
What is ST elevated myocaridal infarction? (STEMI)
- Most severe type of heart attack
- Artery supplying blood to heart becomes blocked
- Fibrinolytic drugs are preffered for STEMI treatment because they can achieve reperfusion unlike drugs from other classes
- They act by converting plasmiogen to plasmin which cleaves fibrin (results in clot dissolution and restoration of blood flow to tissues)
54
What are the 3 lines of defence in the immune system?
1st line of defense: physical and chemical barriers (eg skin, mucuous membranes)
2nd line of defense: internal cellular and chemical defense (eg inflammatin, phagocytosis)
3rd line of defense: immune response (specific defenses targetting pathogens)
55
What is the innate immune system?
bodys natural nonspecifc defense system that repsonds to pathogens immediately, without prior exposure or learning. includes the 1st and 2nd lines of defense
56
what is the adaptive imune system?
bodys specific immune resposne, activated when a pathogen surives the 1st and 2nd lines of defense; learned through expereince and involes the thrid lineof defense (eg antibodies, t-cells)
57
What is leukopoiesis?
process by which uncommited stem cells in bone marrow give rise to various blood cells and platelets
58
How are platelets formed in the bone marrow?
plateltes develop from megakaryocytes in the bone marrow, which breaks apart and release platelts into the circulation
59
How are neutrophils, monocytes and basophils formed?
progenitor cells for neutrophils, monocytes and basophils give rise to these cells, which are then found in circulation
60
Where do lymphocytes come from?
derived from their own lineage of lymphocyte stem cells in bone marrow, which give rise to lymphocytes in the circulation
61
What are basophils and mast cells named after?
basophils and mast cells are named after their structure/morphology and how they stain
62
What is the function of basophils?
function in inflammatory reactions and allergies, release heparin (an anticoagulant) to slow blood clotting and histamine (a vasodilator) to increase blow flow to to tissues; common allergens inclqude ragweed and dust mite faces
63
Where are basophils found in the body?
basophils are found in circulation in low numbers, making up less then 1% of the total white blood cells (WBC)
64
what is the diff between mast cells and basophils?
mast cells similar to basophils but are found in tissues, not in the blood
65
What is the morphology of neutrophils?
segmented nucelus with 2-5 lobes
66
how do neutrophils stain under a microscope?
have cytoplasmic granules that stain kind of pink with hematoxylin-eosin staining
67
How abundant are neutrophils in the blood?
neutrophils are most abundant leukocyte, making up 54-62% of total white blood cells (WBC)
68
What is the main function of neutrophils?
play a key role in immunity; early first responders to infections and are involved in phagocytosis, where they ingest and kill 5-20 bacteria during their short lifespan (1-2 days)
69
What happens during the first/ second step of neutrophil extravasation?
neutrophils roll along the endothelial wall (the inner lining of blood vessles); neutrophils are thethered, captured and activated on the endothelial surface, crawl to exit sites on the endothelial cell junctions, moving toward areas of infection , (what cuases the exit sites for neutrophils to open; signals between leukocytes (like neutrophils) and endothelial cells cause the exit sites to open, allowing the neutrophils to mvoe out of the bloodstream into tissue
70
What is the morphology of eosinophils?
have a bilobed nucleus, meaning nucelus is divided into two distinct lobes
71
How do eosinophils stain under a microscope?
have cytoplasmic that stain bright red with certain dyes like eosin
72
How abundant are eosinophils in the body?
make up about 1.3% of the total white blood cells (wbc)
73
What do eosinophils do?
are involded in defense against parasites; help to fight parasites found in gi tract, lungs, and urinary and genital epithelia by attaching to large, antibody-coated parasites and rleasing substances from their granules to damage or kill the parasites
74
What is an example of a parasite that eosinophils help fight?
Schistosoma is a parasitic disease, recognized by who as the second most devasting parasitic disease disease after malaria, and eosinophils play a role in defending against it
75
How large are monocytes compared to rbcs?
2-3 times larger than red blood cells (RBCs)
76
What percentage of white blood cells do monocytes make up?
monocytes make up about 3-9% of total white blood cells
77
What is the primary function of monocytes?
phagocytic, meaning they ingest and digest foregin particles, pathogens, and debris
78
How are monocytes and macrophages related?
monocytes are the precursors to macrophages. Monocytes are found in the bloodstream, while macrophages are found in tissues, where they preform tissue scavenging
79
What are the main functions of macrophages?
macrophages are primary tissue scavengers, larger and more effective than neutrophils. they ingest about 100 bacteria per lifetime and remove debris, such as old rbcs and dead neutrophils
80
What were macrophages originally called and how were they classified?
macrophages were originally called the "reticuloendothelial system" and were not associated with leukocytes at first
81
When described in diff tissues, macrophages acquire diff names:
- histocytes in skin
- kupfer cells in liver
- osteoclasts in bone
- microglia in brain
- reticuloendothelial cells in spleen
82
what is the mononuclear phagocyte system?
refers to tissue macrophages and their parent monocytes in the blood, which work together in the process of phagocytosis (engulfing and digesting pathogens or debris)
83
What percent of leukocytes in blood do monocytes make up?
make up 3-9% of the total leukocytes in blood
84
How long do monocytes stay in blod beofre moving to tissues?
stay in blood for 8 hours before moving to tissues to differentiate into macrophages
85
What happens to monocytes as they move from blood to tissue?
monocytes enlarge and differnetiate into macrophages during their 8 hour commute from thr blood to tissue, where they preform phagocytosis
86
How large are lymphocytes compared to rbc's?
only slightly larger then rbcs
87
What percentage of white blood cells do lympohcytes make up?
25-33%
88
What percent of lymphocytes are circulating and where are the rest located?
about 5% of lymphocytes are circulating in blood, rest found in tissues encountering pathogens
89
What is the main function of lymphocytes?
lymphocytes play a crucial role in the immune response, which includes:
- naural killer (NK)cells
- t lymphocytes
- b lympohcytes
90
How many lymphocytes are in the adult body?
1 trillion lymphocytes
91
What is the primary function of natural killer cells?
nk cells primarily protect against viral infections and some cancers
92
How quickly do nk cells repsond compared to other lymphocytes?
nk cells respond very quickly, much faster than other lymphocytes
93
How do nk cells destroy target cells?
nk cells destroy target cells (such as infected or cancerous cells, but not pathogens) by cell-cell contact
94
What do nk cell release t aid in the immune response?
release inteferons (ifns) and other cytokines to warn uninfected cells and help enahcne immune defense
95
What is the definiton of antigen?
antigen is a molecule, often found on the surface of a pathogen, that the immune system recognizes as a specific threat
96
Whar are MHC markers?
proteins expressed on surface of cell; display both self and non-self antigens, playing a primary role in the recognition of pathogens and in immune responses; they are also used in self-recognition
97
Where is MHC-I found, and what is its function?
MHC-1 is found on cell surface of all nucleated cells in bodies of veterbrates. plays a role in presenting endogenous antigens to immune system
98
Where is mhcII found, and what its role?
found on macrophages, bcells, and dendritic cell (APCs) it is involved in presenting exogenous antigens to immune system, specifically to helper t cells (CD4+)
99
How are t cells activated?
activated when they have recepots that can recognize antigens presented by antigen presenting cells (APCs)
100
What happens when a helper t cell (CD4) encounters an apc?
if helper T cell encounters an apc with foreign antigen fragment on mhcII, tcell repsonds by secreting cytokines that enhance the immune response
101
Do all helper t cells bind to apcs with foreign antigens?
no, obly helper t cells that recognize the antigen will binf to apc
102
Where does the intial priming or lymphocytes to an antigen occur?
lympth tissues such as spleen. lymph nodes, tonsils and gut
103
What happens in step 1 of tcell activation?
threat: invader enters body
104
What happens in step 2 of t cell activation?
detection: macrophage encounters, engulfs, and digests the invader (eg. a bacterium); macrophage places a piece of invader (antigen) on its surface with the self (MHC) marker
105
What happens in step 3 of t cell activation?
alert: macrophage presents the antigen to helper t cell and secretes a chemcial that activates the t cell; complex set of signals ensures the t cell is responding to non-self (invader)
106
What else happens durng step 3?
helper t cell divides and transforms into effector helper T cell
107
What happens in step 4 of t cell activation?
alarm: effector helper t cell activates
a. cell-mediated (t cell) repsonse: naive cytotoxic t cell activated
b. antibody mediated/humoiural (b cell) reponse: naive b cell acitvated q
108
What happens in step 5 of the cell mediated (t-cell) response?
step 5 building specific defenses; T cell divides into effector cytotoxic t cell
109
What happens in step 6 of cell mediated (t cell response)
effetor cytotoic T (CD8) cells target infected cells
- bind to mhcI and kill infected cells by releasing granzymes (perforin creates pores in target cell, granzymes enter to induce apoptosis)
110
What happens in step 7 of cell-mediated (t-cell) repsonse?
continued surveillance: meory t cells are stored for future surveillnance to reposnd to future infections (cd8 from inside)
111
What happens in step b of b cellr esponse?
step 5: building specific defenses
- naove b cell divides into plasma cell
112
What does step 6 in b cell do?
defense
- plasma cell (effector B cell) secretes antibodies which neutralize foreign proteins (toxins) trigger release of more complement and attract more macrophages
- antibodies target pathofens or toxins outside of cell by bindindng to specific antigen that initated prior events
113
step 7 b cells?
continued surveillance
114
What is the basic concept of clonal selection theory
- many b cell are present at brith, but almost all diff
0 b lymphocytes inherit ability to make antibodies
- each b cell makes only one type of antibody but is intially naive
- exposure to theor antigen makes b cells divide making large population of gentically identical b cell clones
- b cells can make about 2,000 antibodies per second
115
What is primary response?
- first exposure to antigen
- slower and weaker reponse
- produces mostly IgM antibodies
116
What is secondary repsonse?
- occurs after first exposure, due to lymphocyte clones and memory cells
- faster and stronger repsonse
- produces igG antibodies
117
What do antiboides do to pathogenic bacteria?
antibodies do not destroy bacteri a, mark them as targets for immune system attack
118
How many pathogens be attacjed after being targetted by antiboides?
- by innate immune cells (macrophages, neutrophils)
- attaked by complement system (blood proteins defense system)
119
What are complement proteins and where are they found?
complement proteins (c1-c9) are inactive proteins found in the plasma
120
When do complement proteins become activated?
when antibodies mark antigens (like bacteria)
121
What are the 3 complement activation pathways?
1. classic pathway (high level activity triggered by antibodies)
2. alternative pathway (low level, continuous activity)
3. lectin pathway
classic and lectin similar
122
What triggers the classical complement pathway?
high-level activity triggered by antibodies
123
What type of immunity does the complement system belong to?
its part of the innate humoural immunity (always present in blood and ready to act)
124
Can compleemtn system be involved in adaptive immunity?
yes, through adaptive humoral immunity (can be specialized to a pathogen)
125
What are complement proteins made of, and where they are found?
small, mostly inactive proteins found in blood
126
What happens when the complement system is triggered?
proteases cleave specific proteins and start an amplifying cascade of further cleavages
127
What are the two main outcomes of complement activation?
1. massive amplification of the immune response
2. formation of the membrane attack complex
128
The complement pathway?
1. Recognition: c1
2. Activation: c4, c2, c3 (in this order)
3. Attack
- c5
- c6
- c7
- c8
- c9
129
What does the classical pathway of the complement system start with?
- classical pathway stsrts with antibodies and c1 proteins binding to surface of pathogen
- lectin patheay startd with lectins binding to mannose residues on surfsce of pathogen: lectins are carbs biding proteins that are highly specifc for sugar moieties
130
How does the complement cascade work?
1. activation of c1 (classical pathway)
2. c1 catalyzes hydroylsis of c4 into c4a and c4b
3. c4b binds plasma memrbane and is active
4. c3 is cleaved into c3a and c3b
- due to intermeidate step involving splitting of c2
- alternative pathway also results in cleavage of c3 through a diff sequence of events
5. c3b converts c5 into c5a and c5b
6. c3a and c5a stomulate mast cells to rlease histmine
- also serves as chemokines (attract macrophages, neutrophild, monocytes, and eosinophils)
7. c5, c6, c7, c8 and c9 inserted into bacterial cell membrane to form membrane attack complex
131
What is membrane attack complex (MAC)?
large pore that kills bacterial cell throhgh osmotic influx of water
132
What triggers inflammation in tissue?
chemicals signals released by injured tissue
133
What happens when blood vessels widen during inflammation?
redness: increased blood flow brings defensive cells and chemicals
heat: raises metabolic rate of nearby cells to speed up hearing
134
What happens when capillaries become more permeable during inflammation?
swelling: fluid with immune chemicals, clotting factors, oxygenm and nutrients leaks into tissue
pain: limits movedment, which helps area rest and heal
135
What are the 4 signs of inflammation?
redness, heat, swelling, and pain
136
How might the signs of inflammation relate to rice treatment strategy?
rice (rest, ice, compression, elevation)
137
When does inflammation occur?
in response to tissue damage and stress
138
What is acute inflammation?
short-term response to injury, such as bruises or torn tissue
139
What is chronic inflammation?
long-term inflammation assocaited with diseases like arthirtis, obesity etc
140
What happens int erms of a health inflammatory response?
spike in inflammatory signals, followed by resolving signals that return the body to homeostasis
141
What can lead to chronic inflammation?
repeated mild tissue insults that dont fully resolvre, keeping the body in a low-level inflammatory state
142
What is the danger of unresolved inflammation?
it can keep the immune system activated, damaging tissues over time and leading to chronic diseases
143
What is sepsis and the symptoms and treatment?
systemic, whole body inflammation that cuases orgsn dysfunction (potentially fatal); symptoms high fever, rapid pulse/respiratory rate, hypotension, hypoxemiz, oliguria, acidosis
treatment: antibiotics, iv fluids
- low bp, ;ow oxygen, low urine, too much acid in blood
144
What is septic shock?
blood pressure falls so low that organs are not perfused
145
What is a common bacterial cause of sepsis?
lipopolysaccharide (component of gram-negative bacteria)
146
What does lps trigger during a localized infection?
activates the innate immune system
147
What happens when large amount of lps enter bloodstream?
causes release of inflammatory cytokines, leading to widespread inflammation
148
How does the immune system normally work?
by recognizing the diff between self and non-self
149
What are autoimmune diseases?
conditions where the immune system fails to recognize self-antigens and attacks the bodys own tissues
150
What causes autoimmine diseases?
a failure in immune tolerance to self-antigens
151
How common are autoimmune diseases?
there are over 40 types, affecting 5-7% of pop
152
How can an antigen that doesnt normally circulate trigger autoimmunity?
if it becomes exposed to immune system, may be seen as foreign and attacked
153
How can a self-antigen be atlertef to trigger an immune response?
it may combine with a foreign hapten, making it look foreign to immune system
154
How can cross-reactivity lead to autoimmunity?
antobides made against foreign antigens may accidentally bind to self-antigens
155
What role does mhc class II play in autoimmunity?
self antgens presented with mhc II to helper t cells can mistakelny activate them
156
What happens if reg (suppressor) t cells arent active enough
immine system attack self-antigens leading autoimmune
157
What is aids?
human innumodeficiency virus
158
What does hiv infect and destroy?
helper t cells in the gastro, body gets more infections
159
what type of virus is hiv?
retorvirus (carries genetic code in RNA)
160
What does hiv used to copy its rna into dna?
reverse transriptase enzyme
161
What does art stand for?
antiretroviral therapy; blocks transciptase; not cure j contrlls virus
162
Why does hiv return when art is stopped
hiv dna hides in the host dna of memroy helper t cells
163
What cuases most common allergies like hay fever and asthma?
bnormal b cell responses producing ige antibodies
164
What immune repinse occurs if a person is not allergic to allergen
allergen stomulates th1 cells to secrete ifn-gamma and il-2 (normal response)
165
What immune reponse occurs in an allergic person?
allergen stimulates th2 release il-4 and il-13 causing plasma cells to make ige antibodies (instead of normal igG)
166
what is abnormal repsones by T cells?
delayed hypersensitivy hours to days because the reaction is mediated by lumphokines instead of antibodies
- eg contact dermatitis due to poison ivy
167
where is adh synthesized and stored?
made in hypothalamus, stored in posterior pituitary
168
What triggers the release of adh?
increased plasma osmality (dehydration or salt ingestion)
169
What effect does dehydration have on plasma osmality and adh release?
increases plasma osmality, stimulates adh release, increases water reabosoprption in kidneys (increase water so less dehydration)
170
What happens to water in the blood and urine during dehydration?
more water is reabsorbed into the blood means less water in urine
171
What happens during over hydration?
adh release is inhibited less water reabsorbed more water in urine
172
What type of feedback is involded in regulating adh?
negative feedback increased blood volume and decreased blood volume osmality reduce adh release
173
What causes the brattleboro rats inability to produce adh?
mutation in the adh gene, stops adh production
174
What are symptoms of brattleboro rats with no adh?
excess thirst (polydispia)
excessvie dilute urine (polyuria)
175
What conditons do brattleboro rats mimic?
diabetes insipidus: kineys cant conserve water due to lack of adh
176
in normal animal, how does plasma osmality affecr adh and thirst?
as plasma osmality increases, adh increases, thirst also increases to encourgae drinking
177
When do adh levels normally increase in children?
at night, following a circadian rhtym
178
What effect does increased adh at night have on body?
increases water absoprtion in kineys
decreased urine production
179
Why do adh levels at night matter?
prevent waking up to urinate
180
What percent of body water content is in babies?
75%
181
What percent of body water is in women? men? elderly?
50; 60; 45
182
What fraction of body water is intracellular?
2/3
183
What fraction of body water is extracellular?
1/3
184
What are the sources of daily water intake?
drinking fluids and food: 2250 mL
metabolic water production: 250 mL
185
What are the ways the body loses water daily?
urine: 1500 mL
feces: 100 mL
sweat: 200 mL
lungs (exhalation): 700 mL
186
How long can a human survice without water?
rule of 3s; 3 mins without air; 3 hours without shelter; 3 days without water; 3 weeks without food
187
what happenind in iran, 2004?
97 year old woman surive for 8 days without food or water, under rubble of her home earthquake
188
What happenned in mexico city, 1985?
newborn babies trapped in wreckage of hospital after earthquake, rescued 4-7 days later and nearly all survivedl known as miracle babies
189
What are three examples of desert mammales adapted for water regulation?
arabian camels, desert rodetns and antelopes
190
How long can arabian camel survive without water in desert?
several days in a hot and dry environment
191
can arabian camels stay active without water?
Yes, they may still be active under dry conditions
192
Why cant arabian camels halt their kidney function?
their kidneys must keep functioning even in extreme dehydration
193
Where is lipid stored in arabian camel?
in hump
194
Can dry food help arabian camerls get water?
yes, even dry hay provides some water
195
How are arabian camel kidneys adapted for dry environments?
efficient at water recovery
196
How do arabian camels thermoregulate when hydrated?
by panting
197
What is the core body temp range of a hydrated arabian camel?
36.5-38.5 degrees celsius
198
What happens to camel thermoregulaition when they are dehydrated?
stop panting
199
What is the core body temp range of a dehydrated arabian camel?
34.5-40.5 degrees celsius
200
why do camels turn off thermoregulation when dehydrated?
to conserve water
201
How do arabian camels conserve water through body temp changes?
supercool at night
overheat during day night dehydrated camels let theor body temp drop=absorb more heat in monring without needing to sweat; during the day they let is rise=allow using water to cool down
202
What kind of environment is the kangaroo rat adapted to?
small, arid desert environments
203
How does the kangaroo rat lose water?
through high oxygen consumption and respiratory water loss
204
Can kangaroo rats survive without drinking water?
yes, can survive
205
How do kangaroo rats obtain water?
from dry food metabolism
206
Why do kangaroo rats live in undergroud colonies?
mosit air in burrows helps reduce respiratory water loss
207
When are kangaroo rats active?
nocturnal, active at night to avoid daytime heat
208
What type of feces do kangaroo rats make?
very dry (conserve water)
209
What percent of salts is found in fresh water?
0.1% dissolved salts
210
What % of salts is found in human body?
0.9%
211
What% of salts is found in sea water?
3.5%
212
What happens to humans when we drink salt water?
we become dehydrated (because salt water draws water out of cells)
213
Why can marine mammals surive without drinking fresh water?
get water from food (krill, fish, plankton) and metabolism
214
What kind of urine do marine mammals make?
very concentrated urine (to conserve water)
215
How long do grizzly bears hibernate?
for half of the year
216
What do grizzly bears rely on for energy during hibernation?
stored fat reserves
217
How many calroies can a grizzle bear burn per day during hibernation?
up to 8000 cals/day
218
What basic functions do hibernating bears stop doing?
do not eat, drink, defecate or urinate
219
What happens to metabolic and heart rate of hibernating bears?
both are reduced
220
What source provides water for bears during hibernation?
metabolic water from lipid breakdown
221
What happens to urea in hibernationg bears?
recycled to make protien
222
How do bears conserve water during hibernation?
water absorbed from bladder
223
What are kidneys essential for
life: they are essential organs
224
What do kidneys excrete?
metabolic waste products
225
What homeostasis process do kidneys help regulate?
water and electroylte balance and acid base (pH) balance
226
what major blood vessels are associated with the kidneys?
renal artery and renal vein
227
How is urine transported from the kidneys?
through ureters by peristalisis
228
Where is urine stored?
in the urinary bladder
229
what structure drains the urinary bladder?
urethra
230
what is the outer part of the kidney called?
renal cortex
231
What is the inner part of the kidney called?
renal medulla
232
What are found in the renal medulla?
renal pyramids (papillae)
233
What do renal pyramids drain into?
renal pelvis
234
What connects the renal pelvis to the bladder?
ureter
235
What is the functional unit of the kidney?
nephron
236
237
What are nephrons made of?
blind-ended microscopic tubules
238
How many nephrons are in each human kidney?
over 1 million
239
Can nephrons be replaced once lost?
no, npehrons are lost with age and cannot be replaced
240
What is assocaited with all regions of the nephron?
networks of peritubular capillary vessels
241
What percent of nephrons are cortical?
80%; means most of kidneys filtering units are located in outer region and are involved in filtering
242
What percent of nephrons juxtamedullary?
20%, deep into medulla of kidney
243
What are the steps in nephron?
1. blood enters glomerus
2. blood filtered through ephron
3. urine exits out the collecting duct
244
What are the 4 regions of the nephron?
1. Bowman's/glomerular capsule (contains glomerus)
2. Proximal convoluted tubule
3. Loop of Henle
4. Distal convoluted tubule
245
What do collecitng ducts important for?
role in water retention but not normally part of nephron
246
How much fluid enters the bowmans capsule?
180 L fluid/day
247
How much fluid excreted?
1.5 L fluid/day
248
How is urine formed?
1. filtration
-movement of fluid from blood to lumen of nephron
- only takes place in renal corpuscle where glomeruli and bowmans capsule allow for bulk flow of fluid
2. reabsorption
- afte filtrate leaves bowmans capsule, modided by reabsoprtion
- substances in nephron tubules flow back into blood
3. secretion
- molecules are removed from blood and added back into nephron tubule filtrate
249
What does excretion equal?
filtration-reabsoprtion+secretion
250
What makes up the inner layer of bowmans capsule?
podocytes
251
What do pedicels of podocytes form??
intricate interdigitation that creates filtration slits
252
What are filtration slits/diaphragms?
negatively charged strctures that act as filters
253
What percent of plasma protein is in glomerulalr filtrate?
0.03% (compared to 7% in plasma)
254
How often is the entire blood vloume filtered by kidneys?
every 40 mins
255
How much urine per day?
1.5 L.day
256
What happens to most of the glomerular filtrate
reabsorbed into body
257
What determins glomerular filtration rate?
glomerular blood hydrostatic pressure in glomerular capillaries
258
What happens to the arterioles when blood pressure constricts?
afferent artioriole constricts, eferent arterioles dilates
259
What is the average GFR in healthy people?
125 ml/min (combined for both kidneys)!!!!!!
260
In filtration, what are the parts of juxtaglomerular apparatus?
Juxtaglomerular cells: smooth muscle cells in the afferent arteriole
Macula densa cells: sensory cells in region of distal convulted tubule
Mesangial cells: connect juxtaglomerular and macula densa cells ie communicatoin
Sympathetic never fibers: associated with afferent arterioles; redirect blood from kidney to other organ systems
261
What happens in renin-angiotensin system (RAAS)?
1. blood pressure falls
2. juxtaglomerular cells secrete renin into blood
3. rening acts of angiotensin to produce angiotenson 1 (ANGI)
4. angi converted into angII by angiotensin converting enzyme (ACE)
5. angII vascoconstrictor
6. blood pressure increases
stimualtes aldosterone secretion from adrenal cortex
- angiotensin acts with aldosterone to increase salt and water retention by kidneys (increase blood volume)
262
What happens after blood goes through glomerus?
blood vessels continue winding around nephron, blood vessels send more water/solutes into nephron as needed
263
Where is excess K+ reabsorbed from glomerular filtrate?
in proximal convultued tubule into pertibular capallaries
264
What percent of salt and water is reabsrobed across the proximal tubule?
about 65%
265
what percent of the filtrate is reabsrobed throigh the descending loop of henle?
about 20%
266
What happens when tight junctions of the proximal convulted tubule are leaky?
paracellular transport, transporation can also occur through the cell (transceullar transport)
267
What is secretion?
opposite of reabsorption; from peritubular capillaires into tubular fluid
268
What is the summary of secretion?
1. filtration: fluid and solutes leave glomerus and enter bowmans capsule
2. tubular reasbortion:r eturns useful solutes and water to bloodstream
3. tubular secretion: returns secreted solutes and waer to tubules: eliminates wastes from blood
- end result is filtered blood and waste removal (concentrated urine)
269
what is the function of the loop of henle?
creates hyperosmotic environment in the renal medulla to allow urine concentratoin
270
How concnetrated is human urine compared to blood?
4.6 times more concentrated
271
What happens in the descendig loop of henle?
water is drawn out, making it more concetrated
272
What is the osmolality change in the descnednig loop?
goes from 300-1200 mosm/L
273
What happebs in ascneding loop?
salt is transported out, water cannot leave
274
What is the osmallaity change in ascending loop?
decreases from 1200 back to 300 mosm/L
275
what is countercurrent multiplier system?
flow of lfuid in the descneding and ascending go in opp directions, 300-1200 and vice versa
276
What drains into each collecting duct?
several nephrons drain into each collecting duct
277
What hormone affects water reabsorption in the collectikng ducts?
adh
278
What does adh do in collecting ducts?
increases water permeability, allowing water to be draen out by osmosis in blood
279
Where ia water reabsorbed from in the collecting duct?
from the filtrate into the blood via the medullary collecting duct
280
How do collecitng ducts work?
1. adh/vasopressin binds receptor
2. signals cAMP
3. inserts aqp2 on apical side (facing lumen)
4. water absrobed by osmosis into blood
281
What are blood vessle sassociated with the nephron loop?
peritubular capallaries and vasa recta capillary
282
What capillaries are asscoaited with the cortex portion of nephron?
peritubular
283
What capallires are assocaited with the cortex portion of nephron?
vasa recta
284
What is function of vesa recta?
acts as a countercurrent exhance system (not same as counter current multiplier); preserves rhe osmotic gradient
285
What is meant by standing osmotic gradient?
stable diff in solute concentration between the cortex and medulla of kidneys that allows water reabsortion from collecting ducts
286
Where does urine move from?
renal pelvis to ureter; smooth muscle in walls carry out peristalsis
- peristalsis waves move urine toward bladder
- backflow or urine prevented by flap vavle
287
What is urine?
- sterile
- pale to dark yellow
- rapidly populated by bacteria (source of ammonia odour)
- ph range (4.5-8.2)
- sustances not normally found in urine diseases (protein, glucose, blood cells, hemoglobin, bile)
288
What is chronic kideny disease (CKD)?
greater then 10% of people more then 20 million aged 20+ in us have ckd
- most comon among women
- greater 35% aged 20+ with diabetes have it
- greater 20% of people aged 20+ with hypertension have ckd
289
GFR function does it decrease in kiney disease?
YES
290
What is used to trwat kindey failure?
dialysis
291
What is nephrolithiasis?
kdney stones
- hard orbjects formed by kidenys containing crystallized miners/ waste products (concentratoin exceed solbulity)
- incrwased with dehydration
- large stone in calyces or pelvis may stop urine
- small stone less then 5mm can pass into ureter and can cause severe pain
- if meds dont help, may need lithotripsy (shock waves)
- surgery too
292
What are struvite stones?
magneium ammonium phophsate (may be from utis)
293
What is diabetes insipidus characterized by?
- polyria (large urine volume)
- polydipsia (lots of fluids)
- urine is dilute (less then 300 mOsm)
294
What are the two types of diabetes insipidus?
1. central
- inadequate secreiont of adh
- treated with desmopressoin (synthetic adh)
2. nephorgenic
- inability of kidenys to reposns to adh
- invisdiuals must drink lots of water to prevetn dehydraiotn
295
What is hyper and hypokalemia
plasma K+ conentration nromally between 3.5-5mEq/L
Hpyer: greater then 5
- nauea, weakenss and ekg changes
Hypo: less then 3.5
- heart arrythmais and muscle weakness
- diuretics, comiting, metabolic acidiosies, or excess aldosterone secretion
296
What is acute mountain sickness?
indiviausl mvoe to high elveations without being acclimatized (involed the repsiratory and renal systems)
- repsoratroy acclimates thorugh hyperventiakatoin
- kindeys will undergo diuresis resulting in hypovolemia (decreased blood volume) helps mtigate symtpoms
- decreased adh and aldosterone secretoin, and increased natriuretic hormones secretion
Treamtnet: acetazolamide (inhibits carbonic anhydraseP- decreases renal absoprtion of bicarbonate (and water), producing mild diuretic effects and metabolid acidosis
- promotes hyperventilation which adis acclimitazation
297
