2 Physio: Erythron

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RBCs

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- RBCs are circulating corpuscles (not all organelles of cell) which contain oxygen carrying hemoglobin
- main fx:
1. exchange of gases: oxygen and carbon dioxide
2. regulation of blood pH

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erythron

Back 2

all erythroid cells= precursors and RBCs

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mammalian RBC shape

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- biconcave or oval (camelids) discs:
large surface area for gas exchange

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mammalian RBC size

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- average diameter 7 micrometers in man
- 4-8 micrometers in animals

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MCV

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=mean corpuscular volume in femtoliter (10^-15)
- describes volume of 1 erythrocytes
= PCV x10/ RBC
- normo, micro or macrocytic
- RBC parameter

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microcytic

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- small MCV
- 99% of these cases are iron def
- cells cannot produce enough Hb, so max Hb which signals shut off of cell division is not reached, and RBCs continue to divide

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macrocytic

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- larger than normal MCV
- immature RBCs: cells haven't expelled other organelles

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MCHC

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mean corpuscular Hb concentration in %
- describes Hb content in a deciliter of RBCs
= Hb x 100/ PCV
- normo, hypo and hyperchromic
- RBC parameter

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normochromic

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normal concentration of Hb within RBCs= 33%

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hypochromic

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MCHC
- low concentration of Hb
1. iron deficiency
2. immature RBCs

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hyperchromic

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MCHC
- beyond Hb saturation pt
- artifact due to hemolytic sample: lower PCV

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MCH

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mean corpuscular Hb
= Hb content of 1 RBC (picogram)
- inaccurate, not used much anymore
- evaluation like MCHC
- RBC parameter

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immature RBC parameters

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immature RBC parameters
1. macrocytic
2. hypochromic

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Fe deficiency RBC parameters

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Fe deficiency RBC parameters
1. microcytic
2. hypochromic

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anemia causes

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= deficiency in oxygen carrying capacity
1. low RBC count
2. low Hb content
3. malfunctional RBCs
- PCV often low but can be normal

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anemia causes

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anemia causes
1. hemorrhagic
2. hemolytic
*3. dyhemopoeitic: reduced or defectiver erythropoeisis, * majority of anemias

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anemia bone marrow responses

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anemia bone marrow responses:
1. regenerative: reticulocytosis
2. non-regenerative: dyshemopoeitic

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anemia: RBC parameters

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1. RBC size: normo, micro and macrocytic
2. Hb content: normo and hypochromic

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hemorrhagic anemia

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hemorrhagic anemia: acute blood loss (plasma and cells) so PCV initially normal
- regeneration:
1. fluid: 1-3 days, PCV and PP dec
2. PP: 1 week
3. full RBCs: 1-2 weeks
- signs of regeneration in 3-5 days: reticulocytosis, nucleated RBCs
- type: macrocytic, hypochromic, regenerative

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hemolytic disorders

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- increased rate of intra or extravascular destruction
1. blood parasites
2. toxins
3. IMHA
4. inherent defects: sickle cell (common in deer)
- in acute cases, signs of regeneration

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nutritional deficient anemias

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- nutritional deficient anemias
- eg without Fe, cells cannot produce sufficient Hb and keep dividing
- common in piglets
- dyshemopoeitic, non-regenerative, microcytic and hypochromic

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anemia of chronic (inflammatory) disorders

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anemia of chronic (inflammatory) disorders: "slowed down production belt"
- chronic dz, infection (FELV, ehrlichia), inflammations, neoplasms, tissue necrosis
- release of toxins such as cytokines or tumor necrosis factor supress erythropoeisis--> fewer RBCs released (but normal)
- sometimes sequestration of Fe (bad abcesses) in macrophages seen--> Fe trapped --> Fe def--> microcytic, hypochromic
- normally dyshemopoetic, non-regenerative, normocytic and normochromic

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chronic renal dz anemia

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chronic renal dz leading to lack of EPO
- dyshemopoetic, non-regenerative, normocytic, normochromic

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hemorrhagic and hemolytic anemias

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hemorrhagic and hemolytic anemias can become chronic disorders: eg GI ulcers, parasites
- leads to exhaustion of Fe stores after long stimulation
- eventually become non-regenerative anemias

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hemopoesis in fish

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1. bony: mainly in liver, etc
2. cartilagenous: RBCs produced in blood

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removal of aged RBCs

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weakened or damaged RBCs:
1. rupture during spleen passage (tight traberculae) and are absorbed by macrophages -or-
2. selective removed by the mononuclear/ phagocytic system: macrophages in spleen, liver and bone marrow

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recycling of non-Hb RBC parts

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recycling of non-Hb RBC parts is done by macrophages

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globin recycling

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amino acids are released into the circulation are reused for protein synthesis elsewhere

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heme recycling

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1. Fe first removed
2. heme converted to bilirubin
3. bilirubin released into the circulation
4. excreted by the liver in bile juice; yellow color

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transferrin

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- Fe released from heme bound to plasma protein in circulation
- binds strongly with erythroblastic receptors and released into blast cells for Hb synthesis
- can also release Fe into any other tissue, eg liver, spleen, cardiac m

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ferritin

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- Fe bound to intracellular protein of liver, spleen, heart m, etc
- Fe storage form: released when needed

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hemosiderin

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-once ferritin stores are full, excess Fe is storage as nearly insoluble hemosiderin
- liver, pancreas, heart
- can lead to toxic cell damage

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hemosiderin excess

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1. improper diet: common in birds
2. IMHA: eg multiple blood transfusions
3. captive black rhinos:idiopathic

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erythropoeisis and tissue oxygenation

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- erythropoeisis is controlled by tissue oxygenation
1. withdrawl of RBCs
2. hypoxia
3. renal tubular receptors
4. erythropoeitin release
5. stimulation of erythropoeisis bone marrow
6. release of new RBCs

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RBC precursor stimulation

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- EPO stimulates commitment from myeloid stem cell into :
1. CFU/ery
2. rubriblast
- 5days: prorubricyte, rubricyte...
3. reticulocytes

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RBC precursor differentiation

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-RBC differentiation involves:
1. cells become smaller
2. Hb content increases
3. nucleus condenses
4. divisions stop when critical Hb level (33% cell) reached
5. extrusion of nucleus= reticulocyte
6. takes 4-5 days from stem cell to reticulocyte

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reticulocytes

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- immature RBCs, migrate from bone marrow into circulation and mature within 1-2 days
- healthy horses and ruminants only release mature RBCs into circulation
- involves:
1. loss of remaining RNA material
2. loss of Hb synthesis ability
- normally 1-2% of blood

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requirements of erythropoesis

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- erythropoeisis requires adequate:
1. aa's
2. Fe
3. folic acid
4. Vit B 2, 6, 12

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blood challenge gen

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when erythropoesis becomes strongly stimulated via increased EPO release (eg blood loss):
1. more CFU-E are committed
2. mitotic rates increase
3. less mature cells are released from bone marrow into blood

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blood challenge progress

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1. immediately: no inc RBCs and reticulocytes
2. 3-5 days after: more reticulocytes in blood= reticulocytes, eg 25-30% reticulocytes in dog blood
3. 7 days after: peak production, inc reticulocytes
4. 14 days after: full replacement of RBCs

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extreme blood challenge

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- in extreme cases, metarubricytes, rubricytes and rubriblasts are released
- nucleated RBCs appear in blood: buffy coat pink
- although immature, these cells contribute to the oxygen carrying capacity while still increasing their Hb content

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exception of reticulocytosis

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- horses do not show reticulocytosis
- ruminants show mild responses

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fish/ bird/ reptile RBC precursors

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- rubricytes: binucleate
- reticulocytes: uniform heme/ color
- also mitotic RBC precursor cells

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laboratory evaluation of the erythron

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1. hematocrit
2. RBC count
3. Hb content
1-3 usually increase or decrease silmultaneously
4. blood smear and reticulocyte count

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hematocrit lab

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% of whole blood after centrifugation
- unit: L RBC/ L blood

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RBC count lab

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million RBCs/ microliter blood
- performed in counting chambers or automatic counters
- unit: trillion/ L blood

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Hb content lab

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- drop of acid hemolyzes RBC to Hb
- in g/dl
- performed colorimetrically
- SI unit: g/L blood

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blood smear and reticulocyte count

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- subjective evaluation of RBC:
1. morphology: shape, staining, size, presence of erythroblasts
2. % reticulocytes present after special staining

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RBC parameters

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- calculated from 3 primary values:
PCV, RBC count, and Hb content
- important in the description and diagnosis of anemias

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mammalian RBC concentration

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- average 5 million/ microliter in man
- 5-10 million/ microliter in animals

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mammalian RBC content

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- nearly saturated solution of Hb: 33% of an RBC
- enucleate
- non mitochondria
- no golgi or ER

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mammalian RBC metabolism

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- energy gain depends on anaerobic glycolysis
- no mitochondria= no Krebs cycle, no beta oxidation, no ETC= glc dependent

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RBCs in reptiles, fish, amphibians

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- nucleated: non- functional
- larger, oval or almond shaped
- largest: salamander 30x 65 microm

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organs sensitive to hypoxia/ anemia

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organs sensitive to hypoxia/ anemia:
1. nervous
2. kidney
3. liver
4. GIT
- all either because of high metabolism or cell turnover

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clinical signs of anemia

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- may only appear upon exertion:
1. depression
2. tachypnea
3. tachycardia
4. cold limbs: animals with clear claws can also turn blue
5. pale gums
6. muscle tremors/ twitching: due to mem potential becoming more depolarized/ excitable

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anemia: anerobic metabolism

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anemia: anerobic metabolism:
1. dec ATP leads to decreased cell functions
2. inc lactic acid --> metabolic acidosis --> dec Na/L pump via ATPase dysfunction:
a. inc ICF Na leading to cell swelling/ death
b. inc ECF K leading to hyperkalemia which is cardiotoxic (bradycardia)

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anemia: compensation

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anemia: compensation:
1. EPO: doesn't work in dyshemopoeitic anemia
2. hyperventilation: curbs metabolic acidosis
3. vasodilation

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anemia compensation: vasodilation

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anemia compensation: vasodilation:
1. dec peripheral resistance/ BP
2. inc sympathetic: peripheral vasoconstriction, inc HR, inc CO, inc BP
3. inc tissue perfusion

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primary polycythemia

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primary polycythemia (vera): rare
- common in sight hounds
1. lack of feedback control on precursors
2. uncontrolled RBC production: myoproliferative disorder
3. Hct can inc up to 60-70%: high viscosity
4. reduced blood flow, perfusion esp peripheral, capillaries

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secondary polycythemia

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secondary polycythemia: common
- physiological response to oxygen deficiency due to:
1. high altitudes
2. cardiac failure
3. lung diseases
- PCV increases by a few %
- PP unchanged

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relative polycythemia

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relative polycythemia: very common
- not true PC
- caused by:
1. dehydration= fluid loss
2. hemoconcentration
3. typically elevated PCV and PP

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transient polycythemia

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transient polycythemia:
- splenic contraction due to excitement and exercise
- seen in cats, horses, sight hounds
- elevated PCV
- normal PP

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blood type with natural Ab

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- within several weeks after being born, an animal develops Ab against non-present antigens (plasma)
- antigens acquired via food
1. humans: O-A-B
2. cats: A (99% DSH NA), B, (AB rare)h

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human blood types

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1. type A: anti B
2. type B: anti A
3. type AB: no Ab
4. type O: anti A, anti B

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blood types which do not have natural Ab

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- no Ab develop against the non-present antigens unless the animal is exposed to them, typically via a blood transfusion
1. dogs
2. horses: A, C, Q, R, S
3. cattle: B, J, A, F
4. rhesus factor in humans
- only some of the blood types are highly antigenic when infused into a naive recipient

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dog blood antigens

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dogs: 1.1, 1.2, 3, 4, 5, 6, 7, 8
- highly antigenic: 1.1, 1.2, 7

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blood transfusion mismatch: natural Ab present

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- If natural Ab are present (cat, man), the recipient's Ab react with the donor's RBCs:
1. intra-vascular RBC agglutination
2. phagocytosis, rupture of attacked RBCs
3. blockage of capillaries: shock
4. precipitation of excess Hb leading to renal blockage and acute renal failure

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blood transfusion mismatch: natural Ab NOT present

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- if natural Ab not present, the recipient slowly develops Ab after first transfusion with antigenic RBCs
1. first transfusion can show a mild delayed reaction
2. second transfusion with same antigenic RBCs: full-blown immune response against transfused RBCs

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avoiding minor mismatch

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can avoid effects of minor mismatch by spinning blood down and only giving RBCs
- eliminates Ab in plasma of donor

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Blood typing

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- blood typing is the determination of the RBC antigens present in the individual
- done to determine universal donor animals
- eg dog: should be negative for DEA 1.1, 1.2, and 7

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cross-matching

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1. major: donor RBCs and recipient plasma
2. minor: recipient RBCs and donor plasma

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RBC functions

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gas transport:
1. oxygen
2. carbon dioxide
3. bicarbonate

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oxygen transport

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- oxygen binding
- right and left shift
- influence of T and pH
- met Hb
- carbon monoxide

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carbon dioxide transport

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- 33% of total CO2
- binds to globin portions

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bicarbonate

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- carbon dioxide transport as bicarb
- buffering effect
- RBCs contain much carboanhydrase
1. tissue: CO2 diffuses into RBC, CO2 + H2O--> HCO3- + H+
- bicarb diffuses back into plasma
- H+ binds to globin
2. lung: HCO3- diffuses back into RBC
- binds with H+
- dissociates into H2O and CO2
- CO2 expired

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lifespan of RBCs

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- RBCs travel 2.5 km (1.5 mi) everyday (man), squeezing through capillaries half their diameter (bound back due to cytoskeleton)
- survival limited to 4-5 mo in most spp, 2 months in cat and pig, 1 month in birds

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RBC damage

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- due to squeezing through capillaries, membranes become damaged and less flexible
- damaged parts expose new antigens and cannot be repaired
- eventually RBCs are removed or rupture
- everyday approx 1% RBCs die or are removed and have to be replaced to maintain stable RBC numbers