Blood, lymph and immunity Flashcards
Blood is and functions to
Functions to:
Provide internal transport
Regulate
Defend the body.
Blood is composed of cells suspended in plasma. The cells are:
Red Blood Cells (RBCs) or erythrocytes
White Blood Cells (WBCs)
Platelets (Cell fragments)
transportation of blood
Hemoglobin in RBC’s carry oxygen
Nutrients and other compounds are carried dissolved in plasma
Waste removal (CO2, urea, etc) – transports to lungs, liver and kidneys
Hormones – to target organ
WBCs to location of infection
Platelets to location of blood vessel damage (bleeding)
Regulation of blood
Body temperature
Tissue fluid content – provides a reservoir for fluids during dehydration and over-hydration
pH – waste products are usually acidic. Blood buffers these through the actions of three systems:
Bicarbonate buffers
Hemoglobin
Phosphate buffers
Normal blood pH is 7.4 +/-0.05
Defense mechanism in blood
WBC provide immune functions including phagocytosis
Clotting factors and platelets protect against blood loss
Peripheral blood
Blood in vessels
Whole blood
Blood as it is drawn directly from a blood vessel
Plasma vs serum
Plasma the clear liquid in which the cells are suspended
Serum is the fluid left after clotting
Blood volume calculation
Can estimate blood volume of an animal based on its lean body weight
Blood volume in liters is about 6-9% of total lean body weight.
Fit, muscular or hyper animals have greater volume
One reason Greyhounds are used as donors
How much blood can be drawn and when does blood loss cause shock
Usual blood donation is 500 mL
In general, sudden blood loss of > 30% of total volume is a life-threatening situation
Where is blood stored
During rest, the need for circulating blood is lower, so the body stores it in the spleen
Spleen acts like a sponge
When stimulated (exercise, hemorrhage), the spleen contracts and expels the blood back into circulation as needed.
Plasma is
Fluid part of blood
45-78% of the volume of a blood sample
Varies depending on species, exercise and hydration status
About 93% water
Proteins in blood
about 70% of the solutes.
Albumin, globulins, and clotting factors
such as fibrinogen and prothrombin
All proteins, but particularly albumin, contribute to oncotic pressure. Remember - this is important in maintaining vascular volume.
Some of the globulins (gamma) are immunoglobulins which are also called antibodies
Other globulins (alpha and beta) and albumin help to transport lipids and lipid-soluble vitamins (insoluble in water).
Gasses in protein
Oxygen, carbon dioxide, nitrogen
Nitrogen does not have a known bodily function
Electrolytes in plasma
sodium, potassium, calcium, magnesium, chloride, and bicarbonate and phosphate buffers
Colour of plasma and what it can indicate
Tends to be clear, pale yellow in colour in normal animals
White, cloudy appearance indicates high amounts of lipids which may be from a recent fatty meal
Normal to have a pale yellow hue in herbivores – due to plant carotenoids.
A yellow-orange color indicates bilirubin, a breakdown product of hemoglobin
So animals with a hemolytic anemia or liver disease often become icteric
Note that horses have an increase in bilirubin in fasting, this is normal and will give a moderate yellow (not yellow-orange) color to plasma.
White blood cells and granuales
Some have granules (called granulocytes) and are named according to staining characteristics
Others do not have granules (called agranulocytes: monocytes and lymphocytes)
Red blood cells
Red Blood Cells (erythrocytes): carry oxygen bound to hemoglobin
Platelets do what
Platelets: help blood to clot when vessels are damaged
Hematopoiesis is
Means production of blood cells
Continuous process due to continuous loss, use, and replacement
Site of hematopoiesis
Fetus: occurs in spleen and liver
Newborn: occurs in red bone marrow
Older animal:
Most of the hematopoietic tissue (red marrow) in the medullary cavities replaced by yellow bone marrow (mostly fat).
Hematopoiesis continues in ends of long bones and in the flat bones like hip bones, sternum, and ribs.
Liver and spleen can contribute a limited amount, but never become an important site
Hematopoiesis and PPSC
Blood cells all differentiate from a common cell type called the pluripotent stem cell (PPSC)
Various stimuli trigger the PPSC to develop into the type of blood cell required by the body
Cannot reverse the process once differentiation begins (can’t become a RBC then convert to a WBC)
PPSC’s lacking appropriate stimuli will not develop into anything
Hematopoiesis bone marrow
Complete development of most blood cell types occurs in the bone marrow. Cytology of the bone marrow shows populations of cells in various stages of development
Numbers depend on cell type and stimuli bone marrow has received to produce that type
Used to diagnose disease
Except for lymphocytes which mature in lymph tissue (i.e. thymus, lymph node, spleen)
Disease with hematopoiesis
If there is a problem or disease, this may stimulate a large release of cells
Hemorrhage – may stimulate release of RBC’s
Infection – may stimulate release of neutrophils
If the problem is very serious and sudden, immature cells may be released to get as much of the cell type into circulation as possible
Immature cells are not as effective!
RBCs shape and function
Biconcave disks with no nucleus or mitochondria.
Contain the protein hemoglobin
Function to carry oxygen to all tissues of the animal
At tissues, O2 is released and CO2 is picked up and carried back to the lungs
Formation of red blood cells
Erythropoiesis: the production of red blood cells from the PPSC in bone marrow
Stimulated by erythropoietin, produced mostly by the kidney (~85%) in response to low oxygen levels (hypoxia) in the blood.
Initiates differentiation of PPSC into RBC’s
Human erythropoietin used to stimulate RBC production in humans and animals, but often animal’s immune system will destroy it.
Has been abused in horses in an attempt to increase performance
Synthesis of new RBC’s requires iron, folic acid, and vitamin B12
Mature RBCs have no mitochondria, cannot perform Krebs cycle and rely on plasma glucose for energy!!
Why is red blood cell formation important to vet techs
Important to Vet TEchs because RBCs use glucose after blood is collected
Important to separate serum within an hour of collection to prevent errors
Falsely low glucose
Because RBC use up the serum glucose
Falsely high potassium
Because most of the body’s potassium is intracellular it will shift form inside the RC to the serum
Hemoglobin as and does what
A protein composed of two parts; one globin with 4 heme molecules attached = 1 hemoglobin
Heme: each heme molecule has an iron atom portion (Fe++) tha binds to oxygen molecule
Almost all oxygen in blood is bound to hemoglobin
Types of hemoglobin
Hgb that is carrying oxygen attached to each iron molecule is called oxyhemoglobin and appears bright red
Hgb that has no bound oxygen is called deoxyhemoglobin and appears dark red (sometimes purple)
Hgb bound to carbon monoxide is called carboxyhemoglobin and appear cherry red
hemoglobin and gasses
Carrying gasses
Ability of Hgb to carry and hold oxygen depends on pH, temperature, and the concentration of oxygen and carbon dioxide gasses in the air and blood (partial pressures)
Carbon dioxide transport
Some simply dissolves in the plasma
Some is bound to proteins and Hgb (not at the oxygen site)
The majority is transported as bicarbonate
RBCs are very important in bicarbonate formation because they contain an enzyme that catalyzes the formation of carbonic acid
CO2 diffuses into RBC, combines with water to make carbonic acid, then dissociates to produce hydrogen ions and bicarbonate
At the lungs, the reverse occurs, and CO2 is breathed off
Red blood cell life span
RBC life span varies with species and is typically several months
Senescence is the process of aging
As RBCs become senescent, they become smaller, rounder, and less flexible
More easily damaged in the circulation
Old RBCs are removed from circulation and replaced by new ones from bone marrow
Billions of RBCs may be destroyed and produced daily in an animal the size of a human
How are RBC removed from circulation
Extravascular hemolysis
Intravascular hemolysis
Extravascular hemolysis
Macrophages remove senescent or abnormal RBCs from circulation and destroy them
Much of this occurs in the spleen and liver
The main method of removal
Recycled RBC components go where
Amino acids go to liver to make more proteins
Iron is transported by the plasma protein transferrin to the bone marrow to make more RBC
RBC destruction
Heme (red) is broken down to biliverdin (green) then bilirubin (yellow). Bilirubin is
Carried by albumin to the liver
Combined (conjugated) in the liver with glucuronic acid to make it water soluble
Excreted as a bile pigment (yellow)
Some of this is reabsorbed and eliminated in urine
Rest is eliminated in feces
Responsible for providing the normal color of stool and urine
Iron is carried by a plasma protein called transferrin to bone marrow to make more heme
Intravascular hemolysis
RBC destruction within the blood vessels due to mechanical stresses and weakening with age
Contents are released into plasma
Hgb is picked up by a transport protein called haptoglobin and transported to the macrophages in the liver for breakdown
If there is excessive hemolysis all the haptoglobins are filled, Hgb remains free in the plasma (hemoglobinemia) and will be eliminated by the kidneys (hemoglobinuria)
Hemoglobinemia appears as pink or red plasma
Hemoglobinuria appears as red through to pink urine
Both are abnormal findings
Hematocrit and PCV is
Hematocrit (Hct) determined by an automated analyzer, calculates volume occupied by RBC’s from their number and shape.
PCV = packed cell volume.
This is the packed volume of RBCs after centrifugation
Hct and PCV should be similar
Anemia is
Decreased ability of the blood to carry oxygen due to decreased number of RBCs
Three types of anemia
Loss due to hemorrhage, parasitism
Increased RBC destruction
Hemolysis
Decreased RBC production
Often due to chronic condition, sometimes to iron deficiency
Bone marrow suppression
Polycythemia is
Total number of RBCs in circulation is increased
Polycythemia rubra vera
Compensatory polycythemia
Relative polycythemia
Loss of fluid (dehydration) means concentration of RBCs, not absolute number, is increased
Also called hemoconcentration
Increases viscosity of blood and can make heart work harder
Platelets are
Fragments of cells specialized to assist in blood clotting
Small, irregularly shaped, cellular fragments
Do not have a nucleus in mammals
Break off from very large, multinucleate cells (called megakaryocytes) in bone marrow
Process of platelet production is thrombopoiesis
PPSC (Pluripotent stem cell) differentiates into megakaryocyte
Function of platelets
Are involved in hemostasis, or the process of blood clotting
This process prevents leakage of blood from damaged blood vessels
Platelets maintenance of vascular integrity
Maintain vascular integrity
Can attach to endothelium and release endothelial growth factor
Helps keep endothelium healthy
Decreased platelet numbers means leaky capillaries and can lead to petechia (pinpoint hemorrhage) as RBC’s move out through the endothelium into the tissues
Platelet plug formation
Seals small holes in blood vessels
Endothelial damage initiates platelet adhesion to exposed connective tissue and to each other
Platelets then change shape to form pseudopods
Intertwine with each other to form strong plug – platelet aggregation
Platelets role in fibrin formation
Play a part in fibrin formation to stabilize the hemostatic plug
As platelets squeeze together, they release clotting factors to complete the clotting process
There is a complex series of reactions that result in a mature clot
13 clotting factors are involved
Activation of one catalyzes the next step
The end result in conversion of the plasma protein fibrinogen to insoluble fibrin, which forms strands to bind the clot together
Fibrin contracts at the end of this process to assist in pulling the wound edges together
Fibrin also provides scaffolding for the repair of damaged vessel wall and for the granulation tissue
To prevent the clot from becoming too large, other factors are activated that assist in the dissolution of the clot after repair.
Summary of clotting process
Immediate spasm of the vessels to reduce hemorrhage- this is short duration
Platelet plug formation- platelet adhesion followed by platelet aggregation
Clot stabilization- platelets release clotting factors that initiates clotting cascade to turn fibrin into fibrinogen
Clinical applications of platelet formation
Damaged or infected blood vessels (thromboembolism) leading to blockage of vessel (i.e.: stroke)
Anticoagulant rodenticides inhibit Vitamin K, an important factor in the clotting cascade, leading to inability of blood to clot (coagulopathy).
Calcium is also required for blood clotting. Lavender top blood collection tubes contain EDTA to bind calcium, this stopping the clotting process
WBCs are
Mobile defenders against infection and foreign invaders
Pus is an accumulation of leukocytes - purulent
Formed from PPSC’s (pluripotent stem cells) in bone marrow – leukopoiesis
Some develop completely in bone marrow
Other cell lines develop elsewhere, like spleen and lymph nodes
Five kinds, all nucleated in their mature form in circulation: includes monocyte, lymphocyte, neutrophil, eosinophil, and basophil
First classification of WBC
First, the type of defense function they perform
Phagocytosis: cell-eating. The professional blood phagocytes are the neutrophil and the monocyte
Immunity: becoming resistant to infections by foreign organisms. Lymphocytes and basophils
Second way to classify WBCs
Mononuclear: with a single, round nucleus
Lymphocytes
Polymorphonuclear:multilobed, segmented nucleus
Neutrophils, basophils, eosinophils
Pleomorphic: varying shapes without segmentation
Monocytes
Third way to classify WBCs
Agranulocytes:
Two kinds:
Monocytes: large cells that engulf and destroy foreign particles
Lymphocytes: smaller and are involved with immune responses
Excess of either/both is associated with chronic diseases
Granulocytes:
Three kinds (differentiated by their affinity for different stains):
Neutrophils: pale, purple stain (neutral)
Basophils: have very dark-blue staining granules (i.e. they pick up the basic stain)
Eosinophils: red-staining granules (i.e. they pick up the acidic stain)
Neutrophils are
Aka “segs” because they are segmented
Most common WBC of horses, dogs and cats
Not cows or pigs!
Made in the bone marrow in response to infection
Contain lightly-staining cytoplasmic granules
Immature neutrophils are called “band”, nucleus is not segmented
Function of neutrophils
Professional phagocytes (bacteria, debris)
Contain lysosomes (granules) that destroy engulfed material and organisms
They are the first responders against microorganisms
Respond quickly
High numbers in blood are usually associated with infection but can be low numbers if consumed by overwhelming infections!!!
Leave circulation within about 10 hours through a process called diapedesis
Eosinophils are and characteristics
Granulocyte
Named for their red-staining granules
Make up 5% or less of the total WBC count
Characteristics
Segmented with pink-red granules
Granule shape can vary, depending on species, they are very large and easy to see in horses.
Function of eosinophils
Common in skin, lungs, and small intestines
Important in allergies and defense against parasites
Basophils are and characteristics
Granulocyte
Named for the granule affinity for the basic dye which stains things blue
Rarest WBC
Characteristics
Granules may be washed out during staining, so aren’t always visible
Nucleus is segmented
Function of basophils
Granules contain histamine and heparin
Help initiate inflammation and allergic reactions
Maintain blood flow in damaged areas
Histamine causes vasodilation
Heparin is an anticoagulant
Monocytes are and charcteristics
Agranulocytes
About 5% of circulating WBC’s
Characteristics
Migrate into tissues from blood and become macrophages
Largest WBC
Cytoplasm is blue-gray staining
Vacuoles may be present
Nucleus pleomorphic – may be round to horse-shoe-shaped (not segmented)
Monocytes function
Primary phagocytes
Most of their functions occurs in the liver, spleen, lung, and lymph nodes
Act as filters to remove microorganisms, cellular debris, and senescent blood cells
Some are ‘fixed’ and stay in one location
Others are ‘wandering’ and move through the tissues - increase in inflammation
Lymphocytes are and function
Agranulocytes
Major WBC in ruminants and pigs
No phagocytic ability
Formed in bone marrow then mature in lymphoid tissue
Constantly recirculate between tissues and blood
Function
Make antibodies
Kill diseased cells
Lymphocyte Characteristics
Magenta round/oval nucleus with scant, blue cytoplasm
Can be large or small (compared to neutrophils)
Large have more blue cytoplasm and are thought to be younger = lymphoblasts
Small have so little cytoplasm it may be difficult to see – can look like just nuclei
No granules
The lymphatic system includes
Bones
Lymph vessels
Lymph nodes
Spleen
Thymus
Lymphoid tissue
Consists of a series of vessels or ducts and lymph nodes
Lymphatic vessels and tissues are
Lymphatic vessels parallel the routes of veins
They carry excess tissue fluid called lymph to the thoracic region where it empties into the vena cava near the heart
Lymphatic tissue is scattered throughout the body as lymph nodes, the spleen, thymus, tonsils and gut associated lymph nodes.
Function of the lymphatic system
Return of extracellular fluid to blood, including waste materials from cellular metabolism
Filtration and defense against infection
As lymph fluid passes through a lymph node, it filters out microorganisms and cellular debris
Protein and lipid transportation:
Some proteins and lipids are too large to enter directly into circulation
Instead enter by lymphatic vessels
Lymph formation
Lymph starts as excess tissue fluid that is not picked up by blood vessels
Because the blood pressure forcing fluid out of the vessels is stronger than the osmotic/oncotic pressure drawing fluid back into the vessels
Results in an excess accumulation of fluid in the tissues
Blind-ended lymph capillaries within the tissue pick up the excess fluid and join together to form larger and larger lymph vessels
Eventually terminate in the thoracic duct that empties into the vena cava
The lymph vessels have valves within them, preventing back flow
As the lymph moves towards the vena cava, lymph passes through the lymph nodes which filter the lymph and are one of the body’s defenses against infection
Lymph nodes are and contain what
Are kidney shaped and scattered throughout the body
Contain lymphocytes, macrophages and plasma cells
Lymph nodes are called and receive what
Lymphatic vessels which enter lymph nodes are afferent vessels, those that leave the lymph node are efferent vessels
Lymph nodes receive vessels from specific regions of the body so lymph from a specific area always passes through the same lymph nodes
The condition of each node reflects the health or disease of that area
If Infection is present in a specific area, the lymph nodes in that area tend to increase in size to fight the infection
Why are lymph nodes clinically important
Because of their significant enlargement in response to some pathogens they are important indicators of infection
Cancer cells as well as infections may metastasize or spread throughout the body by way of the lymphatic channels
Pathologists examine regional lymph nodes microscopically to determine if the cancer is spreading
Meat inspectors study the lymph system for changes in colour or consistency to determine if part of the carcass should be condemned
Hemal nodes are and does what
small dark red or black structures found in cattle and sheep
Filter blood instead of lymph and are connected to the vascular system instead of lymphatic channels
Located near regular lymph nodes.
Do not mistake them for lymph nodes which have taken up blood following local hemorrhage in the area
Spleen is and what happens if removed
An organ attached to the stomach and associated with both the circulatory system and the lymphatic system.
Body can survive without a spleen- other lymphoid tissue picks up the white pulp functions and other tissue macrophages pick up the red pulp functions. May be some immuno-compromise.
Removal of spleen is called splenectomy
Spleen function
As a storage area for blood
Part of the macrophages distributed throughout the liver and spleen that “clean up”
Phagocytizes fragile worn-out RBCs
Removes foreign material from circulating tissue fluids (both lymph and plasma)
Contains both red pulp and white pulp
White pulp is the localized areas of the lymphoid tissue
Red pulp is the blood vessels, sinuses and associated tissue macrophages
Spleen serves as
Blood storage (remember the spleen has smooth muscle in it that contracts when extra blood is required by the body)
Filtration by tissue macrophages
Removal of senescent blood cells by macrophages
Thymus is and size in young animals
Lymphoid organ located in the cranial thoracic region lying on each side of the trachea
Large in young , progressively gets smaller as animal ages
This is because young animals have a developing immune system.
The thymus is important in the maturation of T lymphocytes
As the animal ages, their immune system becomes fully developed so no longer need the high production of T-lymphocytes.
Tonsils
Found all regions of the body, not just the throat.
Are peripheral lymphoid tissue where mature lymphocytes live
Differ from lymph nodes because they are found:
Close to moist epithelial surfaces (mucosal)
At the beginning of the lymph drainage system not along the vessels.
Gut associated lymph tissue
GALT is the lymphoid tissue lining the intestine and makes up over 25% of the intestinal mucosa and submucosa
