Patho Heme

Composition of blood

• 91% water +9% solutes

• 6 quarts (5.5L in adults)

Chief functions of blood

• delivers substances needed for cellular metabolism

• waste removal

• defends against microorganisms & injury

• maintenance of acid-base balance

what is the percentage of how much plasma takes up of blood volume?

50-55% of blood volume

definition of plasma

liquid portion that contains organic & inorganic elements

what does plasma consist of?

• albumin

• globulins

• clotting factors/proteins

albumin function

• function as carriers

• controls the plasma unction pressure

globulins

• carrier proteins & immunoglobulins

clotting factors/proteins function

• promotes coagulation

• mainly fibrinogen

general info of erythrocytes (RBCs)

• most abundant cells in blood

• responsible for tissue oxygenation

• biconcavity and reversible deformity

• 100-120 day life cycle

MOST abundant cells in blood are?

erythrocytes (red blood cells)

how long do erythrocytes live for?

100-120 days

granulocytes general

• has a nucleus w/ many lobes

• membrane-bound granules in their cytoplasm

  • their granules contain enzymes capable of destroying microorganisms

• inflammatory & immune functions

• capable of ameboid movement (diapedesis)

diapedesis definition

ameboid movement

neutrophils

• defined as phagocytes in early inflammation

• phagocytic component

• polymorphonuclear neutrophil (PMN)

eosinophils general

• ingest antigen-antibody complexes

• induced by IgE hypersensitivity

• increase in parasitic infections

basophils

structurally & functionally similar to mast cells

monocytes

• immature macrophages

• once mature → they make up the mononuclear phagocyte system (MPS)

lymphocytes

mature to T cells, B cells, plasma cells

Lymphoid organs

• primary lymphoid organs

• secondary lymphoid organs

what do primary lymphoid organs consist of

bone marrow, thymus

what do secondary lymphoid organs consist of

• spleen, lymph nodes, tonsils, Peyer patches

• Liver also has lymphoid function

What is the largest lymphoid organ

Spleen

Spleen function

• fetal hematopoiesis

• cleanses blood

• intruders immune response

• destroys aged cells

• blood reservoir

If someone doesn’t have a spleen, what could this mean?

• inability to clean their blood

• inability to initiate strong immune responses → puts them at a higher risk for getting diseases

• patients are at risk for infection → they must keep up with their vaccine to maintain their immune responses

2 types of bone marrow

• red marrow

• yellow marrow

red marrow

• active/hematopoietic

• primary site of hematopoietic stem cells

• makes up the blood components of our body

• found in primarily flat bones in adults (34%), vertebrae (28%), cranium and mandible (13%), and sternum and ribs (10%), and humerus + femur (4-8%)

• vascularized

yellow marrow

• inactive

• found in other bones

stem cells for transplants are commonly harvested from?

the flat bones of the pelvis

where do all blood cells originate from?

hematopoietic stem cells

what do hematopoietic stem cells differentiate into

hematopoietic progenitor cells

hematopoiesis definition

production of all the blood cells from pluripotent HSCs

blood cell production is constantly ongoing, and occurring where?

• liver

• spleen of fetus

• only in bone marrow (medullary hematopoeisis)

without the hematopoietic stem cells, what would happen?

you would lose the function to make all blood components (macrophages, platelets, lymphocytes, etc)

aplastic anemia definition

disease that impacts the amount of stem cells

after birth, where is red blood cell occurring ONLY in

the bone marrow

in fetal life, where does blood happen in

liver and spleen

erythropoiesis definition

process of red blood cell development

sequence of erythropoiesis (with cell types)

progenitor cell → proerythroblast → erythroblast/normboblast → reticulocyte → erythrocyte

• with each step, the quantity of hemoglobin increases + the nucleus decreases in size

steps of erythropoiesis when it starts

• #1: Our kidneys sense they’re getting less oxygen 

• #2: They release erythropoietin from the kidneys

• #3: They go over into the bone marrow to produce more erythrocytes

• #4: More erythrocytes go into our bloodstream

• #5: Now that there’s a high amount of oxygen, the kidneys produce less erythropoietin

• #6: Which shuts down production in the bone marrow > lowers RBCS

erythropoiesis regulation

• under control of feedback loop w/ erythropoietin

• causes an increase in red cell production in conditions of tissue hypoxia

DEETE TIS

reticulocytes

• immature RBCs

• not functioning well

what does it mean if there’s a high count of reticulocytes?

• BAD

• this is saying our body is causing us to produce MORE RBCs

• example: anemia may increase creation of RBCs

ribosomes purpose

• they form globulin; which plays a role in oxygen carrying capacity & heme

negative feedback loop in role of erythropoietin

Low red blood count + low O2 in kidneys = ?more EPO is released from the kidneys > goes to bone marrow > bone marrow makes more erythrocytes > RBC is produced > more O2 is produced > kidneys produce less EPO when there’s enough O2

where is heme synthesized

via mitochondria

globulin comes from?

ribosomes

what does erythropoiesis rely on to synthesize?

hemoglobin (Hb) synthesis

hemoglobin is what part of the erythrocyte

• oxygen-carrying protein of the erythrocyte

• 2 pairs of polypeptide chains???

globulins are made up of?

• 2 pairs of polypeptide chains

• most common in adults: 2 alpha and 2 beta cains

the nucleus is absorbed as what starts to transform?

the cell

what forms heme

4 colorful iron-protoprophyrin complexes

each heme carries what

• one molecule of oxygen

heme is bound to what

reduced ferrous iron (Fe2+)

methemoglobulin

• non-reduced ferrous iron (Fe2+ that cannot bind oxygen)

  • some drugs cause an excess of ferric iron and can cause methemogloblinemia

• doesn’t allow our RBCs to carry oxygen effectively

reduced ferrous meaning

• you may have an enzyme deficiency that doesn’t allow us to produce enough of ferrous iron

when we have an excess in ferric iron, what does it turn into

methemoglobin

PUT NUTRITIONAL REQUIREMENTS LATER ON WHEN ITS ACTUALLY CONFIRMED NEEDED

Who is at risk for having vitamin B deficiencies

people with poor nutrition, alcoholics, those that live in areas with a poor diet

what is iron bound to?

to heme

• in blood or muscle cells

what does iron store?

• stores bound to ferritin

iron cycle overall purpose

allows recycling of erythrocytes controlled by hepcidin

what is the iron cycle controlled by

hepcidin

what is hepcidin

liver produced hormone regulating iron

without a sufficient amount of iron, what are you at risk for

Anemia

approx. 25mg of iron is required daily for what?

erythropoiesis stimulation

• 1-2mg of iron is dietary

who is at the most risk at developing iron deficiency anemia?

pregnant females

• they require more iron to need the needs of the placenta & growing fetus

extra iron gets stored into where?

• liver

• spleen

• transported directly to our plasma

leukocytes undergo what process?

myelopoeisis

myleopoeisis definition

development of granulocytes and monocytes

where do leukocytes mature in

mature in bone marrow

granulocytes become…

2 pools

• functional

• circulating

where are granulocytes stored during myelopoeisis

in blood vessel walls

• they hang around, waiting for something to actually happen so that they can become activated

lymphopoiesis

• development of lymphocytes

• released into blood stream → mature in lymphoid organs

one large megakaryocyte produces what

thousands of platelets

platelet sequence

megakaryoblast → megakaryocyte → platelets

• allows blood to clot properly

megakaryocyte undergoes DNA replication but does not?

divide

what are platelet levels regulated by

thrombopoeitin

red blood cells are regulated by?

erythropoietin

what is thrombopoietin

• a hormone growth factor; produced by the liver w/ action in the bone marrow

• stimulates the production & differentation of megakaryocytes + is the main regulator of the circulating platelet numbers

how many days can the platelets circulate for before losing functional capacity

10 days

hemostasis definition

• the arrest of bleeding by formation of blood clots at the sites of vascular injury

hemostasis; sequence of events

• #1: vascular injury vauses vasoconstriction

• #2: endothelial cell damage leads to platelet adherence and formation of a sympathetic plug

• #3: clotting system activated to form fibrin clots

• #4: fibrin/platelet contracts to form a more permanent plug

transient arteriolar vasoconstriction

the immediate, temporary narrowing of small arteries caused by smooth muscle contraction

• occurs in the first few seconds following tissue injury

what do endothelial cells produce?

nitric oxide and prostacyclin

where do endothelial cells typically adhere to?

the subendothelial matrix of the connective tissue

when there is damage do endothelial cells, it starts to release what?

von-Willebrand factor

• clotting

von Willebrand function

• helps to activate the non-active platelets that are circulating freely in our blood

platelets are all the time circulating in our body, but don’t start clumping until..

• when there is active bleeding

• when hemostasis actually needs to occur

• the endothelial injury activates that > you release Von Willebrand factor → which acts upon those non-active platelets

functions of platelets

• regulate blood flow by inducing initial vasoconstriction

• form platelet plug to stop bleeding

• activate coagulation cascade to stabilize platelet plug

• initiate repair process (clot retraction, clot dissolution)

platelet activation process (when there is damage to vessel)

• #1: adhesion to damaged wall

• #2: activation → degranulation

• #3: aggregation; as platelet-vascular wall and platelet-platelet adherence increases

• #4: activation of clotting system activated+ development of an immobilizing beadwork of platelets and fibrin

blood clot definition

beadwork of protein (fibrin) strands that stabilizes platelet plug

intrinsic pathway

• clotting pathway that is activated when factor XII (Hageman factor) contracts subendothelial substances exposed by vascular ijnjury

extrinsic pathway

• clotting pathway that is activated when tissue thromboplastin is released by damaged endothelial cells

common pathway of clotting factors IMPORTant

• activation of factor X proceeds to clot formation

• 10 AND 10A

what happens during clot retraction?

• fibrin feedback shorten

• becomes denser & stronger to pull/approximate the edges of the injured vessel and site of injury

• facilitated by large numbers of platelets within the clot

fibrinolytic system (lysis of blood clots) consist of what

• plasminogen and plasminogen

• fibrin dehydration products

what is the erythrocyte life span of older adults like

• normal, but erythrocytes are replaced more slowly

  • caused by iron deficiency

    • iron depletion

    • decreased total serum iron, iron-binding capacity, and intestinal iron absorption

  • lymphocytes function decreased

  • humoral immune system = less responsive

Anemia

reduction in the total number of erythrocytes in the circulating blood or in the quality or quantity of hemoglobin

• impaired erythrocyte production

• acute/chronic blood loss

• increased erythrocyte destruction

• combination of the above

anemia physiologic manifestation

reduced oxygen-carrying capacity; hypoxemia