Pathophysiology: Key Concepts

• Thyroxine is not a neurotransmitter.
• Glycine serves as an inhibitory neurotransmitter.

Cushing's Disease vs. Cushing's Syndrome

• Cushing's disease arises from a pituitary adenoma that stimulates excessive ACTH secretion.
• Cushing's syndrome involves hyperadrenocorticism, often caused by Cushing's disease or other tumors.

Key Facts

• Cellular edema can result from improper ADH secretion.
• Traumatic brain injury can lead to vasogenic cerebral edema due to BBB injury.
• Antioxidants are categorized as extracellular, intracellular, enzymatic, and non-enzymatic, based on location and action.

Neoplastic Transformation Stages

• Initiation: Irreversible DNA damage causes mutation.
• Promotion: Leads to benign tumor formation.
• Progression: Causes the tumor to become malignant.

Angiogenesis and TNF alpha

• TNF alpha is angiogenic and is an inflammatory mediator
• Angiogenic factors include TGF, VEGF, PDGF, and angiopoietin.
• Oncogenes, such as RAS or MYC, promote growth.

Diabetes Insipidus

• Diabetes insipidus is a condition marked by excessive urine production and impaired water retention.
• It is due to ADH deficiency (central) or kidney cell resistance to ADH (nephrotic); the origin may be idiopathic.
• Clinical signs include polyuria, polydipsia, weight loss, and neurological symptoms.

Functions of Histamine and Serotonin

• Vasodilation
• Increased vascular permeability
• Bronchoconstriction
• Pain
• Tachycardia
• Activation of lymphocytes

Adhesion Molecules

• Leukocytes, endothelium, and platelets are cells where adhesion molecules are found.

Acid-Base Balance Disorder

• Metabolic acidosis is the acid base balance disorder caused by myocardial infarction.

Bicarbonate Ions

• Bicarbonate ions are reabsorbed, and Na is excreted.
• Carbonic anhydrase facilitates carbonic acid formation in renal tubular cells.

Vomiting and Acid-Base Balance

• Metabolic alkalosis can result from vomiting due to loss of HCL (acid).
• It can occur due to excessive sweating (in horses) or hyperaldosteronism (increased K+ excretion).

Congenital Hypothyreosis

• In congenital hypothyroidism, it arises secondary to TSH deficiency.
• It leads to disproportionate dwarfism.

Insulin Resistance

• Insulin resistance is when cells don't respond to insulin stimulation, thus not taking in glucose.
• Causes of insulin resistance: Cushing's syndrome, obesity, genetic predisposition, hypertension, chronic hyperinsulinemia, Ig against insulin receptors, and acromegaly.

Acromegaly

• Acromegaly results from hypersecretion of growth hormone after the epiphyseal plates close,
• Its origin may involve a pituitary adenoma (often in old tom cats) or mammary gland hyperplasia (dogs).
• Symptoms include massive hypertrophy in the lips, pharynx, soft tissues, thick skin, polyuria, and polydipsia, leading to DM and hyperglycemia in cats.

Clinical Signs of Cushing's Syndrome

• Clinical signs include hypertension, hyperglycemia, increased blood cholesterol, abdominal distention, fragile, dry skin, dull hair, reproductive disorders, polyuria, and polydipsia.
• Cats may show lethargy, obesity, and skin infections
• Ferrets might have urination disturbances, aggression, and swollen nipples/vulva.

Inflammation

• It's a protective response of vascularized tissue to injury.
• Its goal is to dilute, isolate, remove injury causes, and repair the affected tissue
• Inflammation involves cellular and vascular events, characterized by increased cells, proteins, and fluids in interstitial tissues.

SIRS

• SIRS is an exaggerated defense response to a stressor and may develop during sepsis, pancreatitis, trauma, or severe bacterial infection.

Possible Outcomes of Inflammation

• Abscess
• Potential progression from acute to chronic inflammation
• Scar formation (healing by fibrosis)
• Resolution

Neoplasm

• Neoplasm means abnormal cell growth that lacks biological purpose, is irregular, disorganized, and unresponsive to control mechanisms.
• It can either be benign or malignant.

Characteristics of Malignant Tumors

• Metastasis
• Invasion of adjacent areas
• Cell variation in size and shape
• Rapid growth
• Necrosis (if the blood supply is poor)
• Poor differentiation
• Anaplasia

Causes of Metabolic Acidosis

• Consumption of acidic compounds
• Increased acid creation (ruminal acidosis, ketosis, or DM)
• Reduced hydrogen excretion/bicarbonate reabsorption (kidney disease)
• Base loss (diarrhea)

Treatment for Alkalosis

• Increase the acid uptake or decreasing the base level.

ROS Physiological Processes

• ROS help in cell growth, activation of receptors and protein synthesis, and aid in gene expression.
• Pathologically, they oxidize molecules, impair cell function, cause cell death, display antimicrobial/cytotoxic action and oxidative stress

Consequences of Oxidative Lipid Damage

• Altered membrane permeability and fluidity
• Compromised cell integrity
• Generation of toxic lipid peroxidation byproducts

Myasthenia Gravis

• Produced antibodies target Ach receptors, preventing Ach from attaching and inhibiting nerve impulses.
• Main symptoms: rapid/intense fatigue, difficulty holding the neck, tiredness in chewing, strabismus, drooping eyelids, and breathing disturbances

Interstitial Edema

• Caused by impaired CSF outflow, sometimes due to meningitis, hydrocephalus, or subarachnoid hemorrhage

Puerperal Paresis in Cows

• Caused by hypoparathyroidism where PTH inadequately responds to bone tissue.
• Results in severe hypocalcemia, hypophosphatemia, muscle weakness, and paresis

Hyperphosphatemia

• Pathophysiological mechanisms include excessive phosphate intake.
• Decreased phosphate kidney excretion (renal failure, hypoparathyroidism)
• Phosphate shift from cell-interior to the exterior

Vitamin A Toxicosis

• Causes anorexia, thick skin, malformation, and premature closure of the physis in growing animals.

Pellagra

• Pellagra (Black tongue) is caused by B3 deficiency
• Pellagra manifests as mouth sores, diarrhea, dementia, vomiting and dermatitis (3D).

Most Important Extracellular Buffer

• Bicarbonate

Hypoparathyroidism

• Injury to the PT gland or its removal.

Insulinoma

• It involves a pancreatic Beta cell tumor continuously producing insulin regardless of blood glucose.
• Clinical signs of insulinoma include lethargy, seizures, loss of coordination

Endocrine Disorders

• Hypoglycemia (voir karine explication)
• Causes nervous system disorders

ROS Formation

• ROS are formed in aerobic conditions.

Incorrect Statement

• Malignant hypercalcemia is often in cats with neoplasia and in dogs with pituitary adenoma.

Tumors

• PTHrP is produced by lymphocytes in cases of malignant neoplasia like anal sac adenocarcinoma, lymphoma, and sq c carcinoma.

Hyperadrenocorticism

• Hyperadrenocorticism, also called Cushing's syndrome, is an endocrine disease due to prolonged elevation of glucocorticoids in blood.
• It may result from overproduction of cortisol because of a pituitary or adrenal tumor and glucocorticoids.

Anabolic Hormones

• GH
• Insulin
• Estrogen
• Progesterone

Addison's Disease

• Hyponatremia (hypotension, bradycardia, hypovolemia)
• Hyperkalemia (impaired heart rate, muscle weakness)
• Stress intolerance
• Hypoglycemia
• Inappetence

Free Radical

• Hydrogen peroxide is a free radical, yes.

Exudate

• Exudate is composed of leukocytes and proteins.

Metabolic Alkalosis

• Compensatory mechanisms, reduce respiratory rate, use buffer systems and renal compensation

Migratory Patterns of Carcinoma

• Carcinoma migrates through lymphatics.
• Sarcomas mainly migrate through blood vessels.

Oxidative Stress

• Oxidative stress results from imbalance between ROS production and removal by antioxidants.

Glucocorticoid Actions

• Cortisol stabilizes the lysosomal membrane to prevent proteolytic enzyme breakdown.
• Glucocorticoids reduce vascular permeability, preventing transudate and exudation, leading to reduced edema.
• They diminish neutrophil/macrophage migration and release of inflammatory mediators, stabilize lysosomal membranes, decrease capillary permeability.
• They suppress the immune system by decreasing lymphocyte reproduction, reducing both T cell amount and antibodies.

Pendulous Abdomen in Cushing's Syndrome

• Intrabdominal fat accumulation
• Muscle wasting
• Hepatomegaly (enlarged liver)

Uncontrolled Cell Growth

• Activation of oncogenes (ex: RAS gene)
• Inactivation of tumor suppressor genes (Ex: P53)

Myxoedema

• Myxoedema happens in hypothyroidism
• Dermal and cutaneous edema with protein/mucopolysaccharide deposition. Typically located under the tongue, on the limbs, or in the larynx/pharynx.

Acute Inflammation - Vascular Phase

• Vasodilation
• Increased blood flow = transudate and leakage = edema
• Increased vascular permeability
• Stasis of blood flow (decreased blood flow)

Hypocalcemia

• Hypoparathyroidism
• Kidney failure
• Injury
• metabolic alkalosis
• vitamin D deficiency

Catabolic Hormones

• Glucagon
• Cortisol
• Catecholamines

LAD

• Inherited genetic disorder causes inability of leukocyte adhesion to vascular walls with deficiency/failure in AMS expression.
• Increased leukocyte number in blood is present without ability to migrate through capillary to inflammatory site.
• Repeated bacterial infection and severe inflammation results.
• Affects Humans, dogs (Irish setter), and cattle

Thyrotoxicosis (Hyperthyroidism)

• Excess production of thyroid hormones triiodothyronine and thyroxine occurs from an abnormally functioning thyroid gland.
• Can be caused by pathology within the thyroid gland (primary hyperthyroidism),
• Increased sensitivity of thyroid gland to TSH stimulation, and excessive synthesis of T3/T4 hormones.
• Or stimulated by excessive TSH in circulation (secondary hyperthyroidism)

Pituitary Dwarfism

• Hereditary condition.
• Deficiency in growth hormone (GH)/other pituitary hormones.
• It's caused by atrophy/cystic degeneration of the anterior pituitary.
• Affected animals that are 2-5 months of age show proportional growth retardation, develop woolly coat, hair loss, hyperpigmentation/skin peeling.
• Reproductive issues happen due to disrupted gonadotropin (GN) secretion
• By 3-5 years they become and hairless and also underweight through progressive pituitary failure and development of kidney damage.

Endogenous Causes of Inflammation

• Newly formed molecules/antigens
• Oxidative stress
• Immune reactions

Pheochromocytoma

• Pheochromocytoma signs include high blood pressure, palpitations, weight loss, and sudden blindness.

Angiogenic Factors

• Angiopoietin
• TGF-beta
• PDGF
• VEGF

MODS/SIRS Causes

• Sepsis (severe infection)
• Acute pancreatitis
• Severe bacterial/viral infections
• Trauma (major injuries)

Compensation of Metabolic Acidosis

• Early compensation by the bicarbonate buffer/respiratory system
• Long-term compensation involves renal compensation, using the phosphate/ammonium buffer systems.

BBB

• Semi-permeable highly selective border in the brain
• It filters solutes from blood, allows O2, CO2, glucose
• It consists of endothelium, balsam membrane, tight junctions, astrocytes and their "feet."

Metastatic Process

• By uncontrolled cell growth, either through oncogene activation which can create malignant tumors, that mutations can also change the protooncogenes
• Inactivation by tumor suppressor genes is also means where metastisis ocucrs because their are not stopping cell cycle.

Key points in pathophysiology, including neurotransmitters, Cushing's disease and syndrome, cellular edema, antioxidants, neoplastic transformation, and angiogenesis. Overview of the disease and injury pathophysiology, including factors and stages.