Patho Exam 3

what is inflammation

some type of damage

proceeds healing

steps of inflammation

1. vasoconstrictor

2. vasodilator

3. form exudate

vasocontrict

large to small

increase resistance, slow down, WBC leave

Vasodilation

small to large

more blood in

washing out

more nutrients

serous exudate

fluid (blister) clear

fibrous exudate

clotting occurred

break down, form clot, lay down CT

hemorrhagic exudate

RBC

isolate not spread

purulent exudate

pus → neutrophils

red → grey

chymo exudate

lymph fluid

GI tract

fat absorbed here

milky consistency from the fat

what bind to mast cell type 1 hypersensitive to activate degranulation

IgE

compliment (little pieces that fall off)

Chemical injury (K+, neutrophil)

Physical injury (sensitive to movement)

what leaves the mast cell when its being degranulated

1. histamine

   1. H1 receptor and H2 receptor

2. leukotriene

3. Prostaglandin E (PGE)

4. Neutrophil chemotactic factor

5. Eosinophil Chemotactic factor

6. heparin

heparin from degranulation

contribute to keeping clotting cascade in check

H1 receptor from from histamine form degranulation

• vasoconstrictor => smooth muscle contraction

• endothelium contract (move inward) make spaces bigger between cells

• neutrophil chemotaxis

  • neutrophil have H1 receptor

  • recruit neutrophils when endothelium contracts

• + FB Prostaglandin production

  • make more PGE

what happens when endothelium cells contract

• space becomes larger between cells

• bacteria pass through

  • recruit neutrophils to kill

• fluid out of blood into tissue = extradite

H2 receptor from from histamine form degranulation

• keep inflammation In check

• down regulate

  • decrease neutrophils chemotaxis

  • decrease mast cell degranulation

  • suppress lymphocyte/eosinophils (don’t go crazy)

why decrease mast cell degranulation?

-histamine

-mast cells like land mines (don’t want all to go off, keep local)

neutrophil and eosinophil chemotaxis

call in to kill bacteria

the big guns

neutrophil more abundant

Leukotriens

• same function as histamine

• slower acting

• more H1

• contract

• exudate

• pain

• large body

leukotriene vs histamine half life

histamine- short (do thing then fall apart)

leukotriene- longer half life (slower acting)

Prostaglandin E (PGE)

• increase vascular perm.

• vasoconstrictor only at venue end of capillary

• increase exudate production (increase pressure)

• potentiate pain

  • hurt more, alarm, something wrong

• surprises histamine release

• - FB neutrophils, suppress neutrophil release on lysozymes (keep under control, behave)

what causes vasoconstriction of all capillary vs venual end

all- histamine

venue - PGE

2 ways to start clot

extrinsic and intrinsic

extrinsic clot start

• basement membrane protein - Lipoprotein thromboplastin exposed to blood

• activate stuart factor (inactive)

what is needed for inactive Stuart factor to become active

calcium

active stuart factor

• prothrombin → thrombin

  • by activating prothrombin activator

• thrombin enzyme→ cuts off hydrophilic fibrinogen → hydrophobic fibrin

what does fibrin do

glue platelets together

intrinsic clot start

-inside blood, hageman factor activates stuart factor and compliment

what does heparin do to stuart factor

binds to antithrombin 3, binds to stuart factor,

irreversible

knock this out have to wait to make more stuart factor

plasminogen → plasmin

-thrombin (extrinsic)

-Hageman (XIIa) (intrinsic)

-Kallinkrein

-endothelium release tissue plasminogen factor to activate

Hageman factor actives

• prekallirein activator

  • prekallikrein → Kallikrein

• Kallikrein

  • Kininogen → Bradykinin

what is bradykinin

• vasodialtor

• cause endothelium to contract

  • increase vascular. perm

• causes pain

what activates classical compliment

• plasmin

• Kallikrein

• Hageman

what activates alternative compliment

Antibody-antigen

Gram -

c3

classical compliment

C1 → C4+C2 → C3 → C5-C9

chemotactic (call things in WBC)

opsonization (little pieces fall off, proinflamation)

endothelium contract → exudate

vascular perm.

anaphylactic

if u are feeling confident - draw plasma system activation chart

mast cell degranulation chart

exudate does to what in inflammation

exudate → WBC → cellular

WBC → neutrophils

neutrophils on contracted endothelium

• adhesion molecules

• roll on surface

• get stuck on vascular wall

  • margination

steps of cellular component inflammation

1. margination via ICAMs (intercellular adhesion molecules

2. diapedesis

3. phagocytosis

marginate

tissue → exudate

neutrophil squeeze through lead to diapedesis

diapedesis

crawl from blood creep to tissue

the process whereby the leukocyte squeezes in ameboid fashion across the endothelial cells

phagocytosis of inflammation

• macrophage + neutrophil

  • crawl through kill bacteria in tissue

• healing but don’t heal squleroplotted plate

• cell mediated present antigen

macrophage

• phagocytosis and antigen presentation

  • other names: alveolar mac’s, reticulocytes, dendricytes, Kupffer cell, histocytes

neutrophil

• first line, short lived, phagocytosis, lysozymes, oxygen radical, peroxides, hypoxychlorite

  •   other names: polymorphoneucleocyte, poly, PMN, morph’s

eosinophil

clean up soluble products of inflammation, major basic protein, destroys nematodes

basophil

convert into mast cell, acute inflammation stage

leukopenia

decrease in ALL WBC

neutropenia

decrease in neutrophils

a decrease in what WBC is most common

neutrophils because lots of bacteria infections and WBC and RBC are the most numerous

how long are WBC function for

2 weeks then replace them

2 causes of neutropenia

failure to keep up with production and increased removal from circulation

neutropenia failure to keep up

-turn over (only live so long)

-can’t replace fast enough

-chemotherapy distrupt mitosis of cells including neutrophils

-antibiotics neutrophil

neutropenia increased removal from circulation

WBC in transit leaving circulatory when prolonged bacteria infection b/c neutrophil overworked

-call neutrophils into area w/ neutrophil chemotaxis factor by mast cells

eosinopenia

increased inflammation

mast cell release eosinophilic chemotactic factor

call eosinophils to inflammation

use up

basopenia

• basophils leave circulatory system and become mast cells

• hypersensitivity type 1

  • mast cells mediated with IgE binding (allergies)

  • use up mast cells faster than can replace

what are monocytes converted into

macrophages

what are macrophages and where are they heavily represented and what do they do

are antigen presentors

heavily represented in lymph nodes

pick up stuff that needs to be dealt with that pass through

mononucleosis a result of what?

result of Epstein Barr Virus (EBV) causes increase of WBC to have one nuclei (monocytes)

always around take advantage when immunocompromised

Where does EBV affect

lymph nodes around oral cavity and pharynx

what happens when EBV gets into lymph nodes and how does immune system respond

replicates in oropharyngeal lymph tissue, IgM and IgG fight back

what does EBV do to B cells

transforms B cells so that they act abnormally (virus put their DNA into B cells)

and this stimulates T cytotoxic and T suppressors @ the same time

what happens when T cytotoxic and T suppressors are stimulated at same time?

they proliferate

not typically seen together in high amounts usually inverse

how are T Cytotoxic and TSupressors typically seen

inverse

high TC low TS

or low TC high TS

what happens when TC and TS proliferate

lymph nodes enlarge

hemaptosplenomegaly

liver and spleen accumulate TC and TS

what does liver and spleen usually do

normally sequester blood cells

all steps of EBV

spleen function

ginormous lymph node

2 parts

red pulp RBC (access, if too old remove)

white pulp: WBC

old liver function

used to make RBC

EBV 2 types of cells

transformed B cells and reed-stern berg cells

reed Sternberg cells

T cells, B cells, monocytes

polyploids (triploid (3n) or tetraploid (4n))

very large nuclei

mononucleosis spread and types

self limiting

runcourse then done

ex. rhinovirus (common cold)

Hep. A

EBV

leukemia classifications

acute or chronic (slow)

lymphocytic/lymphocytes/lymphogenous or myelocytic/granulocytes/myelogenous

genous=generated

acute lymphocytic

• occurs in children 2-4

• pre B cells or pre T cells

  • differentiation in pleuropotential stem cell route

what do pre B cells and pre T cells do in acute lymphocytic

• infiltrate brain

  • pass through blood brain barrier

• used to have small cure rate but now its over 90%

why is it hard for hydrophilic drug pass through blood brain barrier

• 2 cell barrier

  • astrocytes + endothelium that line cavity

• anything in blood must pass through

• 4 layers of hydrophobic (hard to get drug into liver)

acute myelocytic

• common secondary cancer to chromosomal disorders

  • trisomomy 21 (down syndrome or klinfelters (XXY) or Turners (XO)

• not just 1 type of mylocytic lineage/patheway affected

• used to be cancer w/ low survivor rate but no survivor rate is high

chronic lymphocytic

• later in life, 50+

• dependent on degree of differentiation

  • well differentiated lymphocyte lineage slow progression (don’t worry)

• B cells converted to cancerous

  • hairy cell, rapid, 6 years to live, severe malignancy

why is >50 at risk for chronic lymphocytic

made so many somatic errors

-mutation in gene

-none reproductive

mean nothing but when you are older and they accumulate you reach a threshold, result in chronic lymphocytic leukemia

chronic mylocytic

• age 30-50

• philadelphia chromosome (tumor cell marker)

  • translocation event occur

    • #22 piece translocated to #9

    • move #22 protoconco and relocate it next to #9 protoonco gene

complications of leukemia

pancytopenia, leukostasis, immuno-imcompentent, tumor lysis syndrome, multiple myeloma,

pancytopenia

all hemapoetic cells decrease

pancytopenia patho

• cancer cells growing take immature leucopblast (which are normal) and crowded out by leukemic cells, lose blast cells

  • loose platelets and megakaryocytic (can’t clot)

cells included in pancytopenia that are crowded out

thrombocytes from megakaryocytes

causing thrombocytopenia because megakaryocytic are crowded out so they can’t fragment into pieces (platelets) so can’t clot

leukostasis

increase blood viscosity , blood becomes thicker, cardiac workload increases so put more demand on heart

immune-Imcompentent

increase in immature immune cells

tumor lysis syndrom

• increase in lysis or destruction of leukemic cells

  • so release lot of stuff

    • hyperkalemic

    • acidosis

    • hyperphospatemia

    • increase in action potention

multiple myeloma causes what

bone diffeciencies

multiple myeloma patho

transformed B cells → not normal plasma cells

what do not normal plasma cells release

• make large amounts IgG and IgA

• make pieces of antibody → light chain pieces accumulate → bence jones protein light chain of IgA and IgG

• secrete IL-13 and IL-6

how are antibodies made

by pieces

FAB and FC are made of light chain + heavy chain pieces

what does increased release of IL-13 do

increases activity of osteoclast cells

erode bone

what does increase release of IL-6 do

increase production of B-cells + plasma cells → replace RBC lines → crowding at red marrow hemapoetic tissues found in flat bone

what is red marrow/hemopoeric tissue found?

flat bones which are cranium, hip, sternum, ribs

why does cranium look like a golf ball

osteoclast pull back create space to release acid and erode bone so pockets of bone are gone

erythropoiesis function

production of RBC that function in o2 delivery

high metabolic consumer of O2

• kidney

  • consumes 20% of cardiac output

    • incharge of hormone that controls erythropoiesis

break down of erythroposises procuction and how failure will affect

90% kidney

10% liver

renal failure impact greatly

live failure won’t affect much

what does erythropoietin induce

erythropoiesis

what does eryhropoieses require for it to occur

• vit B12

• folic acid

• iron to be bound to hemoglobin

issues with iron and hemoglobin

• can cause problem w/ iron

• can cause problem w/ iron attaching to hemoglobin

• problem w/ hemoglobin protein