PHYSIO

Interstitial fluid

________- middle man between blood & the tissues a. bathes body cells b.

Osmolarity

________- total molarity of dissolved particles a. important in maintaining normal fluid volumes
Blood osmolarity too high
Vessel absorbs too much fluid from tissues
Results in High BP & Strained heart/arteries
-Blood osmolarity too low:
Fluid moves into tissuesTissue Edema &  BP
-Blood osmolarity mainly a product of:
1. Sodium ions, Proteins and Erythrocytes
2. Blood levels of these solutes are closely maintained

Leukopoiesis

________- Creation of WBCs ● begins with the Hemocytoblast● proliferation & differentiation is stimulated by: ○ Hematopoietic growth factors aka Colony stimulating factors ■ What cause the differentiation to occur ● Chart: Top Hemocytoblast begins to proliferate & differentiate.

Erythropoiesis

________ is Hormonally Controlled ● controlled hormonally based on blood O2 levels.

Hemolysis

________- Rupture & breakdown of RBCs ● RBCs rupture: ○ release Hb, leaving empty plasma membranes ○ Macrophages digest the membranes ● Hb disposal: ○ can block kidney tubules causing Kidney Failure.

Hemopoiesis

________: Process of creating formed elements ● all formed elements are produced in: ○ Red bone marrow: ■ Reticular Connective tissue bordering on ● wide capillaries: Blood sinusoids ■ from a common stem cell: Hemocytoblast ● a Pluripotent stem cell ○ Pluripotent- Can differentiate in many ways depending on signal of the cell ■ Can be WBC, RBC, platelets, etc.

Erythroblastosis Fetalis

________ or Hemolytic disease of the newborn (HDN) ● Rh- mother carrying Rh + baby.

Viscosity

________- resistance to flow a. whole blood is 4- 5 times as viscous as H2O i.

Macrophages

________ ● Phagocytize: ○ bacteria, dead cells, cell fragments, tissue debris- Anything that needs to be cleaned up ● activate lymphocytes to mount the immune response ○ Activate B & T cells- tell them "something is going on.

Lymphocytes

- (25%)
- smallest, almost all nucleus
- mostly found in: lymphoid tissues
1. spleen
2. tonsils
3. thymus
- Crucial to immune response
- Many different kinds:
1. B cells - give rise to:
plasma cells - synthesize antibodies
2. T cells – act directly against:
a. virus infected cells
b. tumor cells

O2 transport

________ is impaired d /t being weird shapes, sizes, missing heme, etc c. Maintenance /Symptomatic TX: dilute it: drain some off, replace it w /saline.

Colony

________ Stimulating Factors (CSFs) ● CSFs are: ○ Glycoprotein hormones or Paracrines ○ often secreted by mature leukocytes ■ in response to Infections & Immune challenges ● "hey, I need you to make more leukocytes to help me out "● each CSF causes production of a different WBC ○ in response to a different need ■ When looking at the chart, they are specific for a specific kind of WBC.

Thrombocytes

Formed elements: not cells, more correct to call them formed elements a. Erythrocytes: 45 % b. Platelets (________) Not a cell, just a fragment c. Leukocytes i. Granulocytes.

WBC Lifespan

________- Depends on what kind & what it is attacking ● most circulate in blood 4- 8 hours after release from marrow ○ Most reside in tissues & blood is just transportation● another 4- 5 days in the tissues ● shorter during infection- fighting & being used up.

Leukopoiesis Overview

_Hemocytoblast differentiates into either a Myeloid stem cell which produces the bulk of things (all the granulocytes & formed elements) except for the B & T lymphocytes which are produced by the Lymphoid stem cell (highly specialized on that side)

oncotic pressure

Think ________- vacuum pressure that proteins provide.

Blood Types and type of compatibility

transfusion compatibility are based on: ○ interactions between Plasma Proteins & Erythrocytes ○ or interactions between: ■ Antigens (Ag) which are on the surface of the RBC, antigens in this case are embedded proteins that act as identifiers of the erythrocyte ■ & Antibodies (Ab), those are the plasma proteins floating around in the cytoplasm.

Antigens

________ (Ag) ● Antigens= antibody generator- stimulates the body intentionally or unintentionally to induce antibodies.

Hemopoietic Growth Factors

________ ● "Commitment "occurs: ○ once the cell has receptors in place for a specific hormone or growth factor ■ Mechanism of a hemocytoblast obtaining the receptors for a specific hormone is not well understood.

Leukocytes

________ ● only formed elements that are intact cells w /all the organelles ● account for less than 1 % of blood volume- d /t being in bone marrow, lympthatics,

Blood is

connective tissue "cells separated by matrix"
various cells & cell fragments c. suspended in liquid matrix ==Plasma --> lacks collagen & elastic fibers d. dissolved fibrous proteins become visible as fibrous strands during clotting

Interstitial fluid

middle man between blood & the tissues a. bathes body cells b

Blood meets the needs of the body tissues

does not directly drop off substances, but rather acts via Diffusion

Transportation a. transports to cells

i. O2, Nutrients, Hormones

Regulation a. helps maintain homeostasis in all body fluids b. regulates pH i. many blood proteins act as buffers

keeps pH from swinging wildly c. adjusts body temp (delivers heat to skin) d. influences H2O content of cells i. blood proteins prevent excessive fluid loss to tissues

Think oncotic pressure

vacuum pressure that proteins provide

Osmolarity

total molarity of dissolved particles a. important in maintaining normal fluid volumes

pick up O2 in the Lungs

a. deliver it to tissues

Hemoglobin (Hb)

iron-containing protein ● carries O2 & CO2 ● buffers blood ● consists of 4 protein chains Globins (2 beta & 2 alpha chains) ○ each bound to a red heme group

● Erythrocyte Life Cycle

■ birth & death rate = 2.5 million cells/sec
RBCs live about 120 days ○ production & cell death closely controlled by homeostasis

Hemopoiesis

a better look ● Stem cell → committed cells (precursors to precursor cell) ● Cannot differentiate to a different cell line once it is a committed cell ○ I.e

Hemopoietic Growth Factors ● "Commitment" occurs

○ once the cell has receptors in place for a specific hormone or growth factor ■ Mechanism of a hemocytoblast obtaining the receptors for a specific hormone is not well understood
○ "push" the cell toward specialization

Erythropoietin

RBC

Thrombopoietin

Platelets

Colony-stimulating factors

WBCs

● Erythroblasts

○ Protein synthesis happening like crazy, multiply, mostly to synthesize Hb, but also other organelles to create the structure ○ As phase progress, there is Hgb accumulation

When Hgb reaches capacity, eject most of their organelles ○ the nucleus shrivels & leaves the cell ○ now called a

Reticulocyte after nucleus & most organelles have left the cell ■ contains Ribosome clusters ● Stem cell to Reticulocyte takes about 15 days ● If they are needed, Reticulocytes leave Bone marrow ● Enzymes degrade the ribosomes ● become mature Erythrocytes in a few days

● produced at the rate of

2.5 million RBC/second

● Hypoxemia (a big trigger) caused by

○ hemorrhage, altitude, exercise, diet

● causes Kidneys to ↑ secretion of Erythropoietin (EPO) ○ also (10%) secreted by Liver ● in

5 days RBC count rises

Polycythemia

abnormal excess of RBCs that ↑ blood viscosity
1. primary polycythemia or polycythemia vera: issue w/ marrow and RBC
cancer of the erythropoietic line in red marrow: RBC produced are not normal:  O2 carrying capacity, weird shapes, missing components etc
- Hematocrit of 80%, blood volume doubles
- Treatment: dilute it, drain some, replace w/ saline
2. Secondary polycythemia: all other causes
- dehydration, high altitude, blood doping, emphysema(chronic hypoxia stimulates EPO)
- May be an appropriate response to lifestyle (9000 feet elevation of living)
Main danger is increased blood volume, blood pressure, viscosity
- With primary polycythemia blood volume can double
- clogged capillaries
- strained heart

Secondary Polycythemia - all other causes

Dehydration, high altitude, blood doping, emphysema

Anemia ●

O2 carrying capability too low ● a symptom of another problem, is not a disease itself ● S/S fatigued, pale, short of breath, chilled ● causes fall into 3 categories

Hemorrhagic anemia

blood loss a

Acute or chronic

Trauma vs Colon CA or heavy periods

Image

2 year old with cerebral malaria in Congo

GCS 8

hit criteria for Ebola (can share S/S of cerebral malaria) & needed quarantine

Abnormal Hemoglobin ● Thalassemias ○ typically in Greeks, Italians ● 1 of the globin chains is absent or faulty ○ RBCs are thin, delicate, Hb deficient ○ different subtypes depending on which globin chain affected ● range in severity from mild to severe ● those require monthly transfusions ● Image

Pale, translucent RBCs indicative of thalassemias d/t ↓ Hgb content

Sickle-cell Anemia ● hereditary Hb defect ● HbS differs in 1 amino acid of 1 globin in a 146 aa sequence ○ Image

Beta chain 6th position is normally Glutamate but is swapped out for a Valene ■ Have a HgbS (sickle) instead of HgbB (normal)

● at ↓ O2 conditions

○ HbS polymerizes, becomes stiff, & spiky

Sickle-cell is

- Hereditary Hb defect
- HbS differs in one amino acid of one globin
- at low oxygen conditions HbS polymerizes
RBCs become stiff, spiky ○ Agglutinate (clump together), rupture, & clog small BVs ○ tissues become ischemic ■ intense pain ○ triggers further sickling ○ positive feedback w/ more sickling occurring

● people w/ 2 copies of the gene

Homozygous ○ have sickle-cell anemia

● people w/ 1 copy

are Heterozygous ○ have "sickle-cell trait" but not the disease

Antigens (Ag)

stimulates the body intentionally or unintentionally to induce antibodies, Antigens = antibody generator,

● enable body to distinguish

○ own cells from foreigners

● detection of a foreign Ag

○ activates immune response ■ response includes secretion of protein

● An example is in a mismatched blood transfusion

○ recipients Abs bind donors Ags ○ causing agglutination (clumping) of the RBCs

ABO Group ● based on presence or absence of 2 Agglutinogens

○ A & B

Transfusion Reactions ● Transfusion reactions ultimately cause

ranges from mild to life threatening CV collapse ○ Immune reaction ■ Hives, Fever, Respiratory Distress, HoTN

Erythroblastosis Fetalis or Hemolytic disease of the newborn (HDN) ● Rh

mother carrying Rh + baby

● during delivery mom may be exposed to Rh Ag ○ shell form antibodies against Rh

this won't affect this baby but if she gets pregnant again it can be a huge problem

ABO Incompatibility ● Can result from incompatibility of ABO types

○ mom is A ○ baby is type AB ■ Ag is not strongly expressed in fetus (develop more after birth) ■ Ab dont readily cross placenta (like the RH do)

Leukocytes

only formed elements that are intact cells w/ all the organelles ● account for less than 1% of blood volumed/t being in bone marrow, lympthatics, etc cells
(RBCs don’t; Plts are not cells)
- account for less than 1% of blood volume
- the mobile units of the defense system
- they prevent disease by:
1. phagocytosis of invaders OR
2. by forming antibodies and sensitized lymphocytes that destroy a specific invader

● the mobile units of the defense system

only come into play when needed

diapedesis

white cells leave blood vessels, squeezing out between the junctions ○ migrate into the tissues

All

i. leave blood vessels & migrate into tissues ii

● some of the granules are

○ Lysosomes ■ merge w/ Phagosome ■ destroying the invader ● others contain a brew of antimicrobial proteins that kill different invaders

Eosinophils

2- 4%) ● large bi-lobed nucleus, red (acidic) granules ● ↑ in parasitic infections (worms) & allergies bc it eats Ag-Ab complexes that are formed when antibodies bind to an antigen ● Eosinophils arent large enough so they release enzymes that kill parasites (worms) ● weakly phagocytic ● eat Ag-Ab complexes

Basophils

(0.5-1%) ● least abundant, large blue (basic) granules ● ↑ in allergies & inflammation
- secrete wide variety of immune modulators :
1. histamine: a vasodilator
- increases blood flow
- attracts other WBCs
2. bradykinin
3. serotonin
4. heparin
- anticoagulant
- promotes mobility of WBCs

Mast Cells ●

similar to basophils ● granulated, Degranulate to secrete Histamine & Heparin ○ Mast Cell Degranulation Immune Response & Histamine release ■ Responsible for a lot of internal & external allergic responses like flushing, hives, etc

● found in Connective tissue near blood vessels

where they reside ● arise from a different cell line in the bone marrow, are released into the blood in an immature state & then mature in the tissues ○ There has been some confusion about how these are generated, they used to think that they were generated from fibroblasts, now they think they are coming from a cell line outside of the hematopoietic line

Plasma cells

synthesize Antibodies b. Antigen comes in → B cells give rise to plasma cells → antibodies are created

Colony Stimulating Factors (CSFs) ● CSFs are

○ Glycoprotein hormones or Paracrines ○ often secreted by mature leukocytes ■ in response to Infections & Immune challenges ● "hey, I need you to make more leukocytes to help me out" ● each CSF causes production of a different WBC ○ in response to a different need ■ When looking at the chart, they are specific for a specific kind of WBC

Lymphoid Line ● Lymphoid stem cells produce

(Image)

○ the human body is normally covered with bacteria, especially

■ Eyes, Respiratory, GI, & Urinary tracts

most common causes of Death

○ Hemorrhage & Overwhelming infection

Leukemic cells have a high metabolic rate

compete w/ healthy tissue for nutrition b/c of their high metabolic rate ■ Leukemic cells win healthy cells starve

● Image

Small, you can see the thrombocytes surrounding a RBC

Platelets, continued

● platelets form pseudopods (can migrate & move around) ○ He used to think of them as static pieces of yellow rock candy (???)

Clotting factors

promote clotting

Growth factors that stimulate mitosis in

a. endothelial cells, fibroblasts, & smooth muscle

Chemicals that

a. attract neutrophils & monocytes to sites of inflammation i

& that help dissolve clots

resolves everything once control has been established

Formed elements are

1. Erythrocytes: 45%
2. Platelets (thrombocytes)
3. Leukocytes
a. Granulocytes
1. Basophils
2. Eosinophils
3. Neutrophils
b. Agranulocytes
1. Lymphocytes
2. Monocytes

plasma

1. 91.5% water, 8.5% solutes
2. Most solutes are proteins(by wt): produced by Liver
3. Except for hormones and gamma globulins
4. Also contains: Gases, Electrolytes, Nutrients, Enzymes, and Wastes

Erythrocyte Structure

1. Biconcave discs: increase surface area
flexible when squeezing through capillaries
2. No organelles: lost during development
3. Anaerobic glycolysis exclusively: no mitochondria
4. Incapable of protein synthesis and mitosis
5. Plasma membrane has Glycoproteins & glycolipids on CM: Determine blood type

Hematopoietic stem cell RBC steps

(hemocytoblast) develops receptors and leads to proerythroblast (committed)
Erythroblast:
Phase 1: organelles and ribosome synthesis called a basophilic erythroblast
Phase 2: Accumulating ton of hemoglobin it becomes a polychromatic erythroblast
Phase 3: Orthochromatic. Once the organelles start leaving and cells caps out in hemoglobin and all necessary components. Nucleus shrinks and ejectedreticulocyte
with a few ribosomes
Once it leave the bone marrow enzymes degrade the residual ribosomal clusters and it becomes an erythrocyte

Neutrophils are

Neutrophils (50 – 70%) Polymorphonuclear Granulocytes
Most abundant WBC
- phagocytize bacteria and foreign matter
- numbers ↑ in infections
- granules stain acidic (red) and basic (blue)
- some of the granules are:
1. lysosomes that merge with phagosome destroying the invader
2. others contain a brew of antimicrobial proteins

Macrophages two jobs

Two jobs:
1. phagocytize: bacteria, dead cells, cell fragments, tissue debris- anything that needs to be cleaned up
janitors and clean- up crews of the body
2. Also activate lymphocytes to mount the immune response

leukemia

Cancer; Leukopenia: INcre WBC
Cancerous production of WBCs—two types:
1. lymphocytic leukemia
- cancerous production of lymphocytes
- usually begins in lymphoid tissue, spreads
2. Myelogenous leukemia
- cancerous production of myeloid cells
- begins in bone marrow, spreads
- myeloid cells differentiate into many types, multiple cell line types affected—(BEN, monocytes)

Platelets: Thrombocytes

• small fragments of megakaryocytes
• cytoplasm contains:
1. actin and myosin – they contract!
2. ER, Golgi, lysosomes
• synthesize various enzymes
3. mitochondria
• make ATP, ADP
• they secrete:
1. clotting factors - promote clotting
2. vasoconstrictors that cause vascular spasms
3. growth factors that stimulate mitosis in: endothelial cells, fibroblasts and smooth muscle
4. release chemicals that: attract neutrophils & monocytes to sites of inflammation
5. Chemicals that help dissolve clots
• 25-40% stored in the spleen released as needed
• rest live in the blood and have a lifespan 4 - 10 days and travel in the blood stream

anemia

1. hemorrhagic anemia - blood loss (acute or chronic=colon cancer, periods)
2. inadequate erythropoiesis or Hb synthesis due to:
a) nutritional (or iron-deficiency) anemia:
- dietary deficiency of iron, vitamin B12, folic acid (B9)
b) pernicious anemia
- gastric mucosa fails to secrete intrinsic factor
- necessary for absorption of vitamin B12
- may be age or autoimmune destruction of parietal cells
c) renal anemia
- lack of EPO caused by kidney failure, age
d) aplastic anemia
- destruction of red marrow by:
- drugs, radiation or viruses, cancers
- impairs production of all formed elements (global reduction: suspect aplastic anemia in red marrow)
- defects in clotting and immunity
3. hemolytic anemia : erythrocytes rupture prematurely
- Causes:
• Hb abnormalities, mismatched blood, bacterial and parasite infections
• mushroom toxins, snake, spider venoms, drug allergies
• Malaria is a huge killer of developing countries
- Erythroblastosis fetalis: disorder usually results from incompatibility between maternal and fetal blood groups, often Rho(D) antigens—a type of hemolytic anemia

Functions of Blood

1. Transportation
a. To cells: O2, nutrients, hormones
Diffusion: blood  ECF (interstitial fluid) cells
b. Away from cells: CO2, Met Waste, hormones
2. Regulation
a. Helps maintain homeostasis in all body fluids
b. Regulated pH: Many blood proteins act as buffers
c. Adjusts body temp (delivers heat to skin)
d. Influences water content of cells
a. Blood proteins prevent excessive tissue fluid loss
Oncotic pressure: Osmotic pressure exerted by colloids in a solution. Ok to say colloid osmotic pressure but redundant: colloid oncotic pressure
3. Protection
a. Prevents blood loss: blood clots
b. Prevents infection:
a. WBCs, antibodies protect against pathogens

Leukocytes; Two Categories

2 categories:
1. Polymorphonuclear Granulocytes
a. multi-lobed nuclei with abundant granules
b. All leave blood vessels and migrate into tissues
c. All are phagocytic
G BEN (basophils, eosinophils, neutrophils)
2. Agranulocytes
a. spherical or kidney shaped nucleus
b. lack visible granules do not stain
ALM (Lymphocytes, Monocytes

agglutination

Because mismatched blood agglutinates:
- RBC antigens called: agglutinogens
- antibodies against agglutinogens: agglutinins

Thalassemias

- typically in Greeks, Italians
- one of the globin chains is absent or faulty
- RBCs are thin, delicate, Hb deficient
- different subtypes depending on which globin chain affected
- range in severity from mild to severe
- Severe require monthly transfusions
- Pale translucent RBC due to this disorder