Test 2- Circulatory Diseases Flashcards
Pulmonary congestion: Usually the result of heart failure and associated with edema.
can see due to bright red color
Diffuse brownish discoloration of the lungs of a dog with chronic pulmonary edema and congestion secondary to left-sided CHF, Noah‟s Arkive
Pulmonary hemosiderosis
presence of “heart failure cells).
liquid in the cytoplasm
SUBACUTE TO CHRONIC HEPATIC CONGESTION IS USUALLY THE RESULT OF RIGHT-SIDED CHF
Livers are enlarged and exhibit rounded edges
Chronic hepatic congestion: “Nutmeg liver”
Subacute hepatic
Congestion – “Nutmeg Liver
Chronically there is low-grade Hypoxia & ↑ pressure of centrolobular hepatocytes leading to atrophy and necrosis.
Vascular Endothelium
Role in hemostasis
Anti-thrombotic & pro-fibrinolytic in the normal state
Pro-thrombotic and anti-fibrinolytic during injury
Modulates perfusion:
NO relaxes and causes vasodilation
Endothelin causes vasoconstriction
Role in inflammation:
Regulates the traffic of inflammatory cells
Produces pro-inflammatory cytokines
Control angiogenesis and tissue repair
Fluid distribution
Total BodyWater:
65% of total body weight Plasma (5%)
Interstitial Fluid (15%)
Intracellular Fluid (40%)
Transcellular Fluid (5%)
YOUNGER INDIVIDAULS HAVE A LARGER WATER CONTENT
Homeostasis:
“A tendency to stability in the normal body states”
Interstitium
Space between tissue compartments (microcirculation and the cells).
Is the medium through which all metabolic products must pass between the microcirculation and the cells.
Composed of the Extracellular Matrix (ECM) and supporting cells
Extracellular Matrix
Composed of structural molecules (collagen, reticulin, elastic fibers) and ground substance (glycoproteins like fibronectin & laminin, plus glycosaminoglycans, proteoglycans etc..)
Water distribution between plasma & the interstitium is primarily determined by
Water distribution between plasma & the interstitium is primarily determined by the hydrostatic & osmotic pressures differences between the 2 compartments
Starling Forces:
In simple terms, the hydrostatic pressure moves fluid out of the vasculature; the osmotic pressure of plasma proteins (oncotic pressure) moves fluid into the vasculature.
however, if the capacity for lymphatic drainage is exceeded
however, if the capacity for lymphatic drainage is exceeded, tissue edema results
Edema
–Abnormal accumulation of excess extracellular water in
interstitial spaces or in body cavities
– Fluid is outside both the vascular fluid compartment and cellular fluid compartment (i.e.: within the interstitium).
Pathomechanisms of Edema
1. Increased blood hydrostatic pressure (Generalized: e.g.right-sided congestive heart failure (CHF); Localized: e.g.: tightly bandaged limb resulting in venous occlusion.
- *2. Decreased plasma colloidal osmotic (a.k.a. oncotic) pressure**
- –Proteins not absorbed from diet (e.g.: starvation, GI malabsorption).
- –Proteins not produced (e.g.: liver disease)
- –Protein loss (e.g. glomerular disease, Intestinal mucosal damage)
3. Lymphatic obstruction. Damage/ obstruction of lymphatics (e.g.: surgery, neoplasms, inflammation)
4. Increased vascular permeability (Inflammation)
Edema can also be classified as
Edema can also be classified as “inflammatory” or “non-inflammatory” edema.
Inflammatory Edema
Inflammatory: Increased vascular permeability – refers as an “exudate”
Edema fluid in these cases is “protein rich” an exudate
(high protein content (>30g/L), specific gravity (>1.025), total nucleated cells (<7x109L)less than 7,000 cells per μl.
Non-inflammatory Edema
Non-inflammatory (e.g.: edema of CHF; edema of liver failure) – refers to as a “transudate”
Edema fluid in these cases is “protein poor” low protein content (<30g/L), low specific gravity (<1.025), low cellularity (<1.5x109L) less than 1,500 cells per μl.
Gross Appearance of Edema:
Wet
Gelatinous and heavy
Swollen organs
Fluid weeps from cut surfaces
May be yellow
Histological appearance of edema
Clear or pale eosinophilic staining depending on whether is non-inflammatory or inflammatory edema.( inflammatory is pink because it has a high protein content)
Spacesaredistended
Blood vessels may be filled with
red blood cells
Lymphaticsaredilated
Collagenbundlesareseparated
Pitting edema
When pressure is applied to an area of edema a depression or dent results as excessive interstitial fluid is forced to adjacent areas
- takes a while for the tissue to go back to normal after you press in
Hydrothorax: fluid in the thoracic cavity
Heifer, Hydrothorax (idiopathic pulmonary hypertension)
Pericardial effusion – “mulberry heart disease”- (inflammatory edema). Note fibrin strands and cloudy appearance of the pericardial fluid.
ass with Vit E/selinum deficiency
Ascites or hydroperitoneum: fluid (transudate) within the peritoneal cavity. Dog with CHF. From McGavin, 2007.
Ascites, horse with CHF, UCVM
Anasarca: Generalized
edema with profuse accumulation of fluid within the subcutaneous tissue
Submandibular edema (“bottle jaw”), is commonly associated with severe GI parasitism and hypoproteinemia in sheep
EDx: homonchus conortus
Horse, forelimb.This animal had generalized edema due to protein-losing enteropathy. AVC
Clinical significance of edema
Dependent upon: extent, location and duration.
Tissue may become firm and distorted due to an increase in fibrous connective tissue after prolonged edema
Pulmonary edema
Non-inflammatory edema: e.g.: Associated to left-sided congestive heart failure (CHF).
Inflammatory edema: Damage to pulmonary capillary endothelium e.g.: pneumonia
ARDS (Acute respiratory distress syndrome) Sudden, diffuse and direct- increase in vascular
permeability: high fatality rate Followed by pneumonia if animal survives
ARDS
ARDS (Acute respiratory distress syndrome) Sudden, diffuse and direct- increase in vascular
permeability: high fatality rate Followed by pneumonia if animal survives
Pulmonary edema, pig
larger lungs with impressions of the ribs
Pulmonary edema, horse,
pulmonary edema, rat
Chronic pulmonary edema
Most commonly associated with cardiac failure
Alveolar walls become thickened-may lead to fibrosis
Congestion,micro-hemorrhages- and accumulation of heart failure cells
Hyperemia and Congestion
Both terms indicate a local increase in blood volume and flow within the vascular bed.
Hyperemia indicates increase of arteriole-mediated engorgement of the vascular bed. Blood is oxygenated (red). INFLAMMATION
Congestion indicates passive, venous engorgement. Blood is not oxygenated (blue). CONGESTIVE HEART FAILURE, TOURNEQT
Physiological Hyperemia:
Digestion: ↑ blood flow to the GI tract during digestion.
- Exercise: ↑ blood flow to muscles during exercise
- To dissipate heat: ↑blood flow to the skin to dissipate heat and cool down.
- Neurovascular: Involuntary ↑in blood flow to the face (facial hyperemia) as a result of embarrassment or emotional distress common in people with social anxiety.
Pathological Hyperemia
Caused by an underlying pathological process – usually
inflammation.
Arteriolar dilatation occurs secondary to inflammatory stimuli (inflammatory mediators).
Reddening (“rubor”) is one of the cardinal signs of inflammation (tumor, calor, rubor, pain, loss of function).
Often associated with edema
Pathological Hyperemia
Gingivitis, dog
Bulbar and palpebral Conjunctivitis, human
Pathological Hyperemia
Congestion
Passive engorgement of vascular beds caused by a decreased outflow of blood
Since the vascular beds are engorged with poorly oxygenated blood tissues are dark red to blue (cyanotic), depending on the degree of stagnation.
Like other lesions it can be classified according to duration (acute or chronic) and its extend: localized (e.g. isolated area of venous obstruction);
generalized: Systemic change like in CHF.
Gastric volvulus(torsion) in a dog :
Twisting of vessels obstructs gastric veins → severe venous congestion (acute, local, congestion) →
ischemia (necrosis) →loss of endothelial integrity →hemorrhage →shock →death
LOCALIZED CONGESTION
Intestinal volvulus, horse
Colonic torsion, horse
Hemorrhage
Is defined as the escape of blood from the blood vessels (extravasation)
Can be external or internal (within tissues or body cavities)
Causes of Hemorrhage
Trauma
Sepsis, viremia, bacteremia or toxic conditions
Abdominal neoplasia may lead to hemoperitoneum
Coagulation abnormalities (platelet and coagulation factor defects or deficiencies)
Hemorrhage vs hyperemia/ congestion
Hemorrhage- blood is outside the vessel wall
Hyperemia & congestion blood is within the blood vessels
Hemorrhage: Clinical significance
Determined by the location and the severity
e.g.: Profuse blood loss is the most common cause of hypovolemic shock; Hemorrhage in the brain or heart can be fatal.
Hemopericardiumleads to fatal cardiac tamponade.
Hemorrhage by rhexis:
Due to a substantial rent or tear in the vascular wall (or heart).
In humans: aortic dissection, dissecting hematoma: dissection of blood between and along the laminar planes of the media (blood- filled channel within the aortic wall)can result in rupture and fatal hemorrhage
Dissecting aneurysm, Left: pig with Copper deficiency
Hemorrhage by rhexis:
Bottom: Male turkey
Dissecting aneurysm
Hemorrhage by rhexis:
In addition to horses, dissecting aneurysms are also reported in the coronary and renal arteries of young male racing greyhounds
In addition to horses, dissecting aneurysms are also reported in the coronary and renal arteries of young male racing greyhounds – can lead to arterial rupture and fatal hemorrhage
Hemorrhage by diapedesis:
Hemorrhage due to a small defect in the vessel wall or rbc‟s passing through the vessel wall in cases of inflammation or congestion (like in the lungs of animals with left-sided CHF…)
Hemorrhagic diathesis
Increased tendency to hemorrhage from usually insignificant injuries (seen in a wide variety of clotting disorders).
Hemothorax
blood in the thoracic cavity
Hemoperitoneum
blood in the peritoneal cavity
Hemarthrosis
blood within a joint space
Hemoptysis
Coughing up of blood or blood- stained sputum from the lungs or airways.
Epistaxis
Bleeding from the nose.
Petechia (pl. petechiae): up to 1-2 mm in size. Especially found on skin, mucosal and serosal surfaces
Ecchymosis (pl, ecchymoses): Larger than petechia (up to ~1 or 2 cm). As seen in bruise (contusion) or small hematoma.
Suffusive hemorrhage: larger than ecchymosis and contiguous. Serosal surface of the stomach, dog.
Paint-brush hemorrhage: Looks like if red paint was hastily applied with a paint brush. Most common on mucosal and serosal surfaces.
Hemorrhage - Resolution
Small amounts can be reabsorbed
Larger amounts require phagocytosis and degradation by
macrophages
Organizing hematoma: Central mass of fibrin & red blood cells surrounded by supportive vascular connective tissue macrophages will eventually phagocytize this lesion.
Resolution of hematoma
- hemoglobin, red blue
- billirubin, blue green
- hemosiderin, yellow, brown
Hemoglobin (dark red blue color)enzymatically converted to bilirubin (blue-green color) and eventually into hemosiderin (gold-brown color)
Step 1 in Resolution of hematoma
Hemoglobin, red-blue
Step 2 in Resolution of Hematoma
Bilirubin – blue-green
Step 3 in Resolution of Hematoma
Hemosiderin (yellow-brown)
Circulatory Disturbances
Edema
Hyperemia & Congestion Hemorrhage
Hemostasis
Thrombosis,Embolism DIC
Infarction
Shock
Hemostasis
Hemostasis (arrest bleeding by physiological or surgical means). Normal hemostasis is a physiological response to vascular damageProvides a mechanism to seal an injured vessel to prevent blood loss.
It is the result of a complex and well-regulated process which maintains blood as a flowing fluid within the cardiovascular system.
The pathological form of hemostasis is
The pathological form of hemostasis is thrombosis, in which a clot (thrombus) forms within a vessel which is not injured or only mildly injured.
Thrombosis can be viewed as an inappropriate activation of the normal hemostatic process
General components necessary for normal hemostasis or thrombosis to occur:
- Vascular wall (mainly the vascular endothelium)
- Platelets- primary component of the clot/thrombosis
- Coagulation cascade
“ Blood clotting is a physiological necessity whereas thrombosis is a pathological manifestation of blood coagulation”
Normal Hemostasis
After initial injury a brief period of arteriolar vasoconstriction occurs mostly as a result of reflex neurogenic mechanisms and is augmented by the local secretion of factors such as endothelin (a potent endothelium-derived vasoconstrictor).The effect is transient, and bleeding would resume were it not for activation of the platelet and coagulation systems.
Endothelium gets damaged which exposes the ECM;
endothelin
a potent endothelium-derived vasoconstrictor
helps to limit the bleeding
Endothelial injury exposes
Endothelial injury exposes highly thrombogenic subendothelial ECM, allowing platelets to adhere (via GpIb (glycoprotein lb) receptors to von Willebrand factor) and become activated
adhere to exposed ECM via the receptors
Primary Hemostasis
Activation of platelets results in a dramatic shape change (small rounded → flat platelets with ↑surface area) and release of secretory granules [ADP and TXA2] lead to further platelet aggregation (via binding of fibrinogen to platelet GpIIb-IIIa receptors) to form the primary hemostatic plug. This molecules also promote vasoconstriction. Within minutes the secreted products have recruited additional platelets (aggregation) to form a hemostatic plug; this is the process of primary hemostasis- this is the first thing that happens to prevent blood loss!
secondary hemostatic plug
Tissue factor (factor III-thromboplastin) is also exposed at the site of injury.Tissue factor is a membrane-bound procoagulant glycoprotein synthesized by endothelium. It acts in conjunction with factor VII as the major in vivo pathway to activate the coagulation cascade, eventually culminating in thrombin (factor II activated) generation.Thrombin (IIa)cleaves circulating fibrinogen (factor I) into insoluble fibrin, creating a fibrin meshwork deposition (secondary hemostatic plug).Thrombin also induces further platelet recruitment and granule release.This secondary hemostasis sequence lasts longer than the initial platelet plug
What happens after the plug has been made?
Polymerized fibrin and platelet aggregates form a solid permanent plug to prevent any additional hemorrhage.At this stage counter-regulatory mechanisms [e.g., tissue plasminogen activator, t-PA (fibrinolytic product) and thrombomodulin (interfering with the coagulation cascade)] are set into motion to limit the hemostatic plug to the site of injury.
Purpose of Endothelial cells
Endothelial cells are key players in the regulation of homeostasis, as the balance between the anti- and prothrombotic activities of endothelium determines whether thrombus formation, propagation, or dissolution occurs”
Endothelial cells allow the blood to remain in a fluid state, but it can have different functions, such as to cogulate the blood
Coagulation Cascade
Amplifying series of enzymatic conversions; each step proteolytically cleaves an inactive proenzyme into an activated enzyme,
At the conclusion of the proteolytic cascade, thrombin converts the soluble plasma protein fibrinogen into fibrin( an insoluble molecule to a soluble molecule)
Coagulation factors are plasma proteins produced mainly by the liver
Thrombosis
“ Formation or presence of a solid mass (thrombus) within the CV system”
Happens when the vessel is normal or when a minor injury is exaserbated
when hemostasis goes wrong
Thrombus (pl. thrombi):
Aggregate of platelets, fibrin and entrapped blood cells.
Can result in occlusion of the vascular lumen and embolism
It is adhered to the vascular wall as opposite to a blood clot.
Thrombus within the pulmonary artery, cow
in pic: RBC at top and thrombos in the middle
Pathogenesis of Thrombosis
Virchow triad
For thrombosis for occur, you usually need 2/3
1. Endothelial injury
2. Alterations in blood flow
(turbulence or stasis)
3. Hypercoagulability
- ↑in coagulation factors (or ↑sensitivity
to)
- ↓ in coagulation inhibitors
Mural thrombus, left ventricle, Cat
in animals with infection(endothelial damage
Location of thrombi within heart
Atrial thrombus, left atrium(left side of the picture), cat with Hypertrophic Cardiomyopathy (HCM)
- location of thrombi within Cardiovascular system
due to abnormal blood flow and endothelial damage due to hypoxia
Pulmonary thrombosis, dog( can be caused by heartworms or renal/glomerular disease)
Seen in dogs with severe renal glomerular
disease
protein losing nephropathy
Significant loss of Antithrombin III, a major inhibitor of thrombin
Verminous thrombosis – thrombus formation in the cranial mesenteric artery of horses with Strongylus vulgaris infection
friable material attached to the wall
can cause colic
Strongylosis – colon, horse, Cornell files
venious thrombosis
Saddle thrombosis, cat with Hypertrophic Cardiac Myopathy .Thrombus is located in the trifurcation of the abdominal aorta
saddle thrombosis- thrombosis at the trifercation of the terminal aorta;
MOSTLY IN CATS
left sided heart failure
Outcome of thrombi
- Lysis- thrombosis can dissapear
- Propagation- thrombosis can become bigger and bigger
- Embolization- a piece of the thrombosis breaks off and travels in the blood
- Organization/ recanalization- they will be invaded by macrophages, etc and you will have vascularization of new blood vessels and new channels
Recanalization of an occlusive thrombus, cat
this became organized and recanalization- new blood vessels
embolism
If pieces of a thrombus break off from the original mass and sail downstream to lodge at a distant site, that process is called embolism.
embolus
If pieces of a thrombus break off from the original mass and sail downstream to lodge at a distant site, that process is called embolism. The mass that brakes off is called an embolus”
An embolus is any detached intravascular mass (solid, liquid or gaseous) which is carried by the blood to a site distal to the point of origin; most emboli originate from detached pieces of a thrombus, hence the commonly used term of thromboembolism”
Right: Fibrocartilaginous embolism,
dog – spinal cord- results in spinal cord infarcts(areas of necrosis in the spinal cord)
Fat Embolism
Could be a complication of long bone fractures
Right: Bone marrow emboli in pulmonary artery, human –secondary to CPR resuscitation efforts
Infectious causes of thrombosis/ thromboembolism
Bacterial valvular endocarditis in cattle
often involve the right AV valve and can
give rise to septic emboli that will lodge in the pulmonary arteries to inflammation/ abscess Formation(embolicpneumonia).
- friable material attached to the wall
- bacteria from the thrombos can break off and they can get stuck in the pulmonary vein
Thrombotic Meningoencephalitis (TME), steer, Noah’ Arkive Etiology: Histophilus somni(bacteria that is common in cattle) infection – results in vasculitis and thrombosis
if you section the brain, you will see sections of necrosis
Fibrin thrombi within glomerular capillaries, PTAH stain - DIC
Disseminated Intravascular Coagulation (DIC)
Signs of tissue hypoxia, infarction or/and hemorrhage are seen.
“Potentially catastrophic systemic reaction (thrombo-hemorrhagic disorder) in which there is generalized activation of the blood coagulation system”(Not a primary disease because it can be triggered by different things).
Many etiologies including extensive tissue injury, neoplasia, systemic immunologic reactions (e.g. anaphylaxis) and sepsis
- Can lead to ”consumptive coagulopathy” and hemorrhagic diathesis.
- You will have wide activate of the cogaulation cascade
Venous infarction, small intestinal volvulus, pig. Note the intensely congested loops of small intestine undergoing venous infarction.The twisting of the mesentery associated with the volvulus has resulted compression of the arteries and veins of the intestine. Because arterial pressure is higher than venous pressure, some blood can get into the gut but the compression of the thin-walled veins result in backing up and stagnation of blood in the gut.
Infarction
Infarction: “Localized area of ischemic or as a result of hypoxic necrosis in a tissue or organ caused by occlusion of either the arterial supply or the venous drainage”
Venous infarcts are usually intensely hemorrhagic as blood backs up into the affected tissue behind the obstruction
Arterial infarcts
Arterial infarcts are often initially hemorrhagic but become pale as the area of coagulation necrosis becomes evident
Acute pale infarcts, kidney, rabbit. Multiple, pale white to tan pyramidal-shaped infarcts extend from the renal cortex to the medulla.The infarcts bulge above the capsular surface
triangular shaped lesions
Indicative of acute cell swelling.The glistening areas on the right are highlights from the photographic lamps
triangular shaped section
Renal Infarct, HE
again, triangular shape
Microscopically an infarct is
Microscopically an infarct is a focal area of coagulation necrosis
Shock
Shock (Cardiovascular collapse)
- Shock is the final common pathway for a number of potentially lethal clinical events, including severe hemorrhage, extensive trauma or burns, large myocardial infarction, massive pulmonary embolism, and microbial sepsis
- Regardless of the underlying pathology, shock gives rise to systemic hypoperfusion; it can be caused either by reduced cardiac output or by reduced effective circulating blood volume. The end results are hypotension, impaired tissue perfusion, and cellular hypoxia. This may lead to DIC and “multi-organ system failure”.
systemic hypoperfusion
Regardless of the underlying pathology, shock gives rise to systemic hypoperfusion; it can be caused either by reduced cardiac output or by reduced effective circulating blood volume. The end results are hypotension, impaired tissue perfusion, and cellular hypoxia. This may lead to DIC and “multi-organ system failure”.
Types of Shock
- Cardiogenic Shock
- Hypovolemic Shock
- Blood Maldistribution
4.
Cardiogenic Shock
failure of the heart to maintain normal cardiac output
Hypovolemic Shock
Fluid loss due to hemorrhage, vomiting, diarrhea
Blood Maldistribution
Anaphylactic (Type 1 hypersensitivity)
Neurogenic (neurological injury leading to loss of vascular tone and peripheral pooling of blood)
Septic (results from the host innate immune response to infectious organisms that may be blood borne or localized to a particular site).
Septic
results from the host innate immune response to infectious organisms that may be blood borne or localized to a particular site
Pathogenesis of Septic Shock
Most cases of septic shock are caused by endotoxin-producing gram-negative bacilli (endotoxic shock). Endotoxins are bacterial wall lipopolysaccharides (LPS) consisting of a toxic fatty acid (lipid A) core common to all gram-negative bacteria, and a complex polysaccharide coat (including O antigen) unique for each species.
LPS and other microbial substances induce injury & activation of the vascular endothelium plus stimulate (“activate”) WBCs to release cytokinesvasodilation & pro-thrombotic diathesis (DIC).
Brain & heart are very susceptible to tissue hypoxia.
thrombin
necessary to cleaves fibrinogen into fibrin
end result of the clotting cascade
TO MAKE THROMBIN
Thrombosis vs post mortem clot
post mortem clot- bright shiny surface smooth
thrombos- mostly platelets and fibrin; surface is dull and granular; will usally be attached to the wall of the blood vessel
horse that came into ross
lesion of veninmous arteritis or parasties in the thrombi
vena cava thrombosis
in cattle
ruminal acidosis results from
ruminal acidosis does damage to the rumen; bacteria get into circulation and result in abysesses that are close to the caudal vena cava and these can rupture or form thrombosis
PTAH stain
fibrin thrombin within glomerular capillaries
PTAH satin- DIC
What kind of necrosis is associated with isemeic/hypoxia?
Cogulation
What are the three layers of tissue in the arteries and veins and which is thicker the wall of an artery or a vein?
tunica intima, tunica media, and tunica externa
Walls of Arteries are the thickest!
Iron (Perl‟s) stain – Hemosiderin-laden Macrophages* (“heart failure cells”) within alveoli – UCVM.
or siderphages
chronic pulmonary edema with LCHF
Pulmonary congestion: Usually the result of heart failure and associated with edema.
Diffuse brownish discoloration of the lungs of a dog with chronic pulmonary edema and congestion secondary to left-sided CHF, Noah‟s Arkive
Livers of horses with right-sided CHF.
Left: UCVM; Right: Dr. King‟s Show&Tell.
Livers are enlarged and exhibit rounded edges
Chronic hepatic congestion: “Nutmeg liver”
Subacute hepatic
Congestion – “Nutmeg Liver”
Chronically there is low-grade Hypoxia & ↑ pressure of centrolobular hepatocytes leading to atrophy and necrosis
