VPHY 3108 FINAL

what is hematopoiesis and the process

what is hematopoiesis and the process

-production of blood cells in the bone marrow
-hematopoietic stem cell= multipotentiality
1) hematopoietic stem cell divide, make copy of it self
2) cell lose ability to self replicate
3) committed step: turn into progenitor cell
4) committed stem cell= differentiate to erythrocytes, platelet, etc.

order of cell development in hematopoesis

hematopoietic stem cell, progenitor cell, precursor cell (blasts), mature cells

how does age affect hematopoiesis and bone marrow

slower hematopoiesis as age; younger- bone marrow=dense

what are the key factors that support hematopoiesis

macrophage, adipocytes, endothelial cells, cytokines, growth factors= make cell functional

what is the structure and function of erythrocytes

-biconcave discoid shape= max membrane surface so increase gas exchange
-flexible/deformable= prevent damage when enter small spaces like capillaries

what is the general process of erythropoiesis and major factors that simulate and inhibit it

-production of blood cells
-myeloid (stem) cell differentiate into progenitors and precursors after replication
-leave bone marrow
-turn into reticulocytes
-keep dividing till hemoglobin synthesis

-stimulated by hypoxia=trigger EPO (erythropoietin) production that is released by kidney to bone marrow
-stimulated by thyroxine, SCF, growth hormone, androgens, IL
-inhibited by proflammmation cytokines= TNF-a, IL6, estrogen

what is erythrocyte senescent and the 2 types

-elimination of erythrocytes from circulation due to age
-extravascular hemolysis in liver and spleen by phagocytoses
-intravascular hemolysis in blood circulation
-macrophage= recycle components of erythrocyte like iron

hemoglobin

-how well oxygen is transported

hemocrit

percent of blood made by RBC

MCV

-avg blood cell size
normolytic, macrolytic, microlytic

MCHC

-avg hemoglobin size

peripheral blood smear

-see parasite in blood or sickle cell

define anemia and major mechanisms

-decrease in transport of oxygen in blood
-decreased RBC, hemoglobin, hemocrit
-SO increase EPO to increase RBC
-mechanisms= loss of RBC thru hemorrhaging, period, infection, autoimmune disorder, low EPO thru kidney disease

list stages of hemostasis

1. vasoconstriction
2. primary hemostasis-formation of platelet plug= platelet adhesion, activation, aggregation
3. secondary hemostasis- strengthening of platelet plug
4. fibrinolysis- breakdown of clot

primary hemostasis- injury

platelet receptor interact with exposed collagen; vWF released from injured endothelial cell; matrix and plasma form

primary hemostasis- adhesion

platelet adhere to collagen
-GpIb-vWF binding with platelet to resist forces of circulation
-GpIIb- fibrinogen binding

primary hemostasis- platelet activation

-activated by adhesion to matrix proteins, receptor activation
1. shape change
2. release reaction of granules
3. phospholipid metabolism
4. 2 hemostasis reaction
5. activation of fibrinogen receptor

primary hemostasis- platelet aggregation

platelet stick to each other forming plug; mediated by FIBROGEN

secondary hemostasis

-strengthening of platelet plug generating polymerized fibrin clot by coagulation factors

coagulation factors

-plasma proteins (thrombin) by liver, enzymatic factor, non enzymatic factors
-intrinsic and extrinsic pathway

fibrinolysis

-breakdown of clot as not want thrombus to go to brain. but still need healing
-endothelial cells proliferate and repair
-release tPA- activating plasmin from plasminogen to break down polymerized fibrin

key triggers and inhibitors of primary hemostasis

inhibitor- physical barrier, release of platelet inhibitors like nitric oxide and PGE12, medications that are platelet inhibitors like aspirin (COX inhibitor) that decrease thromboxane 2

key triggers and inhibitors of secondary hemostasis

inhibitor
-endothelial cell express thrombomodulin that binds thrombin inactiving
-protein C
-plasma protein and plasmin
-antithrombin

compare main features of primary and secondary hemostasis and fibrinolytic disorder

primary- platelet problem, weeping from site of injury, less excessive ex. pin point hemmorage- petechia, epitaxis, ecchymose
secondary- excessive ex. hematoma, subcutaneous bleeding, hemothorax- bleed longer
fibrinolysis- can have bleeding but mostly lack ex. leukemia

Myelopoesis

-process of making WBC from myeloid stem cell

Lymphopoesis

-process of making lymphocytes from lymphoid stem cell

Identity and describe different types of leukocytes

-granulocytes
1. Neutrophils
2. Eosinophils= little balls of granules that are red
3. Basophils= purple wing purple balls
-lymphocytes= one uniform color due to having a large nucleus
-monocytes= largest

What is the most abundant leukocyte

Neutrophils

What is the largest leukocyte

Monocytes

What is the most rarest leukocytes in circulation

Basophils

Function of neutrophils and mechanism

-1st line of defense
-highly mobile phagocytes
-promote and heal inflammation
-affected by chemotaxis, phagocytosis

Mechanism
-NET- neutrophil extra cellular trap that releases DNA and trap bacteria with granules that kill
-degranulation- mediator within granule that attack when expunged
-phagocytosis- eat bacteria and attack within

Function of eosinophil

-antiparasitic function
-can phagocytose
-inactive mediators from MAST CELLS= allergic/hypersensitive response
-

Function of basophil

-produce mediators in allergic reactions
—histamine= increase vascular permeability, increase smooth muscle contraction
— IL4, IL13= increase IgE production

What leukocyte has a large nucleas

Lymphocyte

Function of lymphocytes

Produce B and T cells
-B cell= from HSC in bone marrow
=antigens
-T cells= from HSC made in bone. Marrow then mature in thymus

Function of monocyte

-precursor to macrophage and dendritic cell
- waste disposal, initiation And resolution of inflammation
-osteoclasts

Predict changing in leukocyte numbers reflect major disease states

-increase in leukocytes
—bacterial= high nuetorpilhs
—viral= high in lymphocytes
—autoimmune disorder
-decrease in leukocytes
—something wrong in bone marrow
—cancer= block function
—drug=chemotherapy
—toxin

Describe the basic differences between the innate and adaptive immune response

-innate= inherited, non specific, pre made immune response
-adaptive= specific immune response

What is the 2 types of innate immunity

2 Types
1. External defense= epithelial/mucosal barrier like digestive tract, pH, secretions
2. Internal defense= proteins, phagocytes, feverm complement system, interferons- increase immune activity like phagocytosis, NKT

Describe adaptive immunity and types

-changes with exposure
-meditated by lymphocytes that are exposed to specific antigens
-NK cells
-B cells
-T cells= all types
-cell mediated= T cells destroy host cells
-humoral immunity= antibodies made my B cells

List cardinal signs of inflammation

SLIPR- swelling, loss of function, increase temp (fever), pain, redness

Mechanisms of initiation of inflammation to cause signs

-initiate nonspecific phagocytosis by WBC
-activate mast cells in damaged area
-mast cell= release histamine and more cytokines
1) Dilate blood vessels (redness, fever)
2) increase capillary permeability (swelling)
3) Chemotaxis- blood phagocytes attracted by cytokines (diapedesis of neutrophils and monocytes)

What leukocytes does the mechanism of inflammation by phagocytosis and how

Neutrophils and monocytes by engulfing foreign material and releasing cytokines to recruit more leukocytes

Phagocytes and mechanism of defense

1) marophage first to encounter and release cytokines to attract more
2) neutrophils arrive first (pus form)
3) monocytes turn to macrophage
3) T lymphocytes for specific immunity

Compare and contrast function of B and T cells

B cells- antibody receptors and humoral immunity
T cells-cell mediated immunity

B cell and Humoral immunity

1) Memory cells
2) plasma cell
Function in antibody production
-Ab receptors for specific Ag binding
then make:
-memory cells
-plasma cells that release antibody
1st exposure= IgM then IgG
then memory B cells wait
2nd exposure= IgM and robust IgG
then Ab bind Ag
-trigger complement cascade
-neutralize
-opsonize
Can use T helper cell to induce B cells to make antibody

T cell and Cell mediated function

-Killer T cells (CD8)= kill pathogen
-Helper T cell (CD4)= increase response of both T and B cell
-Regulatory (suppressor) T cell= decrease response of killer T and B cells; protect against autoimmune disease development
-Lymphokines= cytokines= ILs, IFNs
-CD4+ (helper T subset)= regulate adaptive immune response
-Natural Killer T cell (innate)= secrete perforins (make pore and lysis); granzymes (trigger apoptosis)

What antibodies produce primary immune felines to antigen

IgM

Identify and define different classes of antibody and their function

Antibody= immunoglobulin
- 2 long heavy chains and 2 short light chains
G- secondary immune response
M- primary immune response
A- main external secretions in mucosal
E- allergy, mast cells, histamine
D- lymphocytes
(GAMED)

Active immunity

require prior exposure to specific antigen to develop own antibody
-receive live virus, killed virus, recombinant viral proteins

Passive immunity

given active immunity- antibodies

Antigen

foreign molecules that cause adaptive response in B and T cells
-proteins, glycoproteins

Epitopes

portion of antigen that is recognized by antibody or T/B cell receptor- binding part of antigen

Paratope/ Antigen binding site

part of antibody recognizing Ag (bind)

Explain the concept of self-tolerance in immunity

-ability of immune system to recognize self-produced antigens as non threat while mounting response to foreign substances
-B and T cells= specific antigen receptors= BCR and TCR
---big diversity because of DNA rearrangement (recombinases)

types of tolerances (3)

1. lymphocyte tolerance
2. central peripheral self tolerance
-T cell tolerance
-B cell tolerance

lymphocyte tolerance

-BCR and TCR- recognize antigen, generated at random, recognize self antigen
-need to do this to not attack own cells=autoimmune disease
===self-reacting lymphocytes prevented from mounting response to specific self antigen

Central peripheral self tolerance: T cell

1. differentiate lymphocytes that recognize self and non-self
2. bind self-antigen strongly= apoptosis in thymue
3. weak= T reg
4. escape= deleted/supressed

Central peripheral self tolerance: B cell

1. differentiate lymphocytes that recognize self and non-self
2. bind self-antigen= B CELL RECEPTOR EDIT= give another chance to not be self antigen
3. escape= deleted OR ANERGY- state of inactivation

consequences of autoreactive T and B cells

increase inflammation in body causing bowel disease, etc.

Pathophysiology of immune-mediated disease

BCR and TCR recognize self antigen and attack causing inflammation to own cells

Risk factor of autoimmune disease

age, environment, genes, genetic, diet

risk of treatment of autoimmune disease

decrease immune response

treatment of autoimmune disease

IL17 and TNF- increase inflammatory response, block cell to cell interactions

Consequences of specific immune-mediated disease based on tissue/organ
-brain
-liver
-hand
-skin

MS, Type 1 diabetes, rheumatoid arthritis, psoriasis

what are the different types of hypersensitivity reaction and specific kind

Type 1,2,3,- antibody mediated hypersensitivity reactions
Type 4- T cell mediated hypersensitivity reaction

Pathophysiology of Type 1 and example

=antibody mediated
-1st exposure- activate CD4 helper T cell, B cells make IgE, IgE bind to mast cell to find allergen
-2nd exposure- allergen bind to IgE on mast cell, mast cell activated, release vasoactive mediators like histamine= edema, vasoconstriction
=allergies

Pathophysiology of Type 2 and example

=antibody mediated
antibody cause:
1. opsonization/phagocytosis
2. inflammation by active complement
3. cellular dysfunction
=autoimmune hemolytic anemia, pephigus vulgaris (skin)

Pathophysiology of Type 3 and example

=antibody mediated
-B cell make IgG
-Ag-Ab complex bind tissues
-activate complement
-recruit/activate neutrophils
-neutrophil mediated tissue damage (NET)
ex. systemic lupus erythematosus, rheumatoid arthritis

Pathophysiology of Type 4 and example

=cell mediated
-delayed type
---CD4 T cells activate APC, release cytokines, inflammation
-T cell mediated cytoxicity by CD8 cell
ex. TB test, contact dermatitis, poisen ivy

Describe major functions of kidney (8)

1. Eliminate waste
2. water balance
3. electrolyte and mineral balance
4. acid base balance
5. conversion of nutrients
6. endocrine functions
7. excretion of wastes and toxins
8. water homeostasis

glomerular function

filtration for filtrate formation composed of water, ions, small molecules

tubular function

reabsorption of substances that pass through glomerulus, secretion, excretion; water balance, electrolyte regulation, acid base homeostasis

PCT function

reabsorb glucose, Na, Cl, K, Ca, phosphate; secrete ammonium and creatine

descending loop of henle function

reabsorb water

ascending loop of henle function

reabsorb Na and Cl; reabsorb ammonium, sodium chloride

DCT

reabsorb Na, Cl

collecting duct

reabsorb Na, Cl; secrete ammonium, hydrogen ion, and K

Define glomerular filtration rate

rate fluid moves from plasma to glomerular filtration (urinary space)

Glomerulus made of what (3)

1. basement membrane
2. podocytes
3. fenestrations

forces that make glomerular filtration work (3)

1. glomerular blood hydrostatic= push out to filter flood
2. blood colloid osmotic pressure= albumin drives fluid in
3. capsular hydrostatic pressure

glomerular filtration let molecules pass based on

size and charge

GFR impacted by (4) and mainly depend on

1, blood volume
2. cardiac output
3. number of functional glomeruli
4. vessel constriction and dilation
depend on renal plasma flow

what passes through the glomerulus freely and needs reabsorption in the renal tubule (PCT)

small hydrophilic molecules
1. glucose
2. amino acids
3. LMW proteins

where are most electrolytes and minerals reabsorbed (Na, Cl, Ca)

proximal tubule

Tubule and water balance: concentration ability

reabsorb water in excess of solutes in the filtrate

Tubule and water balance: diluting ability

reabsorb solutes in excess water in filtrate

Collecting duct= how does it alter filtrate osmolality

control water resorption through ADH=AVP, mediated through aquaporin= water out of filtrate

AVP=ADH- effect, where is it from and where does it act

secreted by posterior pituitary, act on collecting duct, water resorption, needs medullary hypertonicity

renin-angiotensin-aldosterone

mineral corticoid; made in adrenal gland; act on renal tubule, function to Na,Cl in and water also go in, K out

polyuria

increased frequency of urination

polydipsia

increase thirst

anuria

no urination

oliguria

decreased frequency of urination

azotemia

increase non protein nitrogenous compounds in blood

cause and effect of azotemia (pre renal and post renal)

-decreased GFR
-increase serum creatine
-increase urea nitrogen
-pre renal= decrease GFR
-post renal= block in excretion, UTI

Uremia

urea in blood

difference in test of glomerular and tubular disease

tubular= urinalysis
glomerular= GFR

creatinine

freely filtered; if increase levels in urea= decrease GFR

urea nitrogen

freely filtered; showed GFR