Pathophysiology of primary HT:

? renal blood flow

Pathophysiology of primary HT, main:

A. Sympathetic nervous system (SNS)

B. Renin-angiotensin-aldosterone system (RAAS)

C. Natriuretic hormones

D. Inflammation

E. Insulin resistance

F. obesity

Pathophysiology of Acute Coronary Syndrome (ACS):

Atherosclerotic plaque partially obstructs coronary blood flow -> Stable plaque -> ?

Pathophysiology of Acute Coronary Syndrome (ACS):

Atherosclerotic plaque partially obstructs coronary blood flow -> Unstable plaque with

ulceration or rupture and thrombosis -> ?

Pathophysiology of Acute Coronary Syndrome (ACS):

Atherosclerotic plaque partially obstructs coronary blood flow -> Unstable plaque with

ulceration or rupture and thrombosis -> Acute Coronary Syndrome (ACS) -> Transient

ischemia -> ?

Pathophysiology of Acute Coronary Syndrome (ACS):

Atherosclerotic plaque partially obstructs coronary blood flow -> Unstable plaque with

ulceration or rupture and thrombosis -> Acute Coronary Syndrome (ACS) -> Sustained

ischemia -> ?

What is the disease?

• It is caused by gradual luminal narrowing and hardening of the arterial walls, so that the

affected vessels cannot dilate in response to increased myocardial demand associated with

physical exertion and emotional stress

• With rest, blood flow Is restored and no necrosis of myocardial cells results

Pathophysiology of ?:

• The thrombus is less labile and occludes the vessels for a prolonged period, such that myocardial ischaemia progresses to myocyte necrosis and death

• The duration of ischaemia determines the size and character of the infarction

Pathophysiology of MI:

– If the thrombus breaks up before complete distal tissue necrosis has occurred, the infarction will involve only the myocardium directly beneath the endocardium (?)

Pathophysiology of MI:

– If the thrombus lodges permanently in the vessel, the infarction will extend through the myocardium all the way from endocardium to epicardium (?)

Cellular injury of ?:

1. Cardiac cells ischaemia -> 20 mins -> irreversible cellular death

2. Anaerobic metabolism

Lactic acid accumulation -> acidosis and suppress conduction -> heart failure

3. Oxygen deprivation is accompanied by electrolytes disturbance -> Diminish heart pumping ability

4. Arterial occlusion -> release catecholamine and induce dysrhythmia and heart failure

Angiotensin II released -> peripheral vasoconstriction and fluid retention -> increase cardiac workload and cause cardiac artery spasm

5. Remodeling of myocardium (scarring and myocyte hypertrophy)

Frank-Starling mechanism:

• The greater the stretch of cardiac muscle fiber, the greater the force of contraction -> ? CO

Frank-Starling mechanism:

• Plateau of contraction power -> congestion -> ? effectiveness in a failing heart

Beta blockers further divided into:

– Inhibit beta1 (heart) and beta2 (bronchial) receptors

– Cause bronchoconstriction due to unopposed parasympathetic tone

– E.g. Propranolol (Inderal) and carvedilol (Dilatrend)

Beta blockers further divided into:

– Act mainly on beta1 receptors (but not absolute)

– E.g. atenolol, bisoprolol (Concor), metoprolol (Betaloc)

Example of Calcium Channel Blockers:

are relatively selective for vasculature

⮚ e.g. amlodipine (Norvasc) and nifedipine S.R. (Adalat Retard)

Example of Calcium Channel Blockers:

are more selective for the heart

⮚ e.g. verapamil (Isoptin), diltiazem (Herbesser) which also has some effects on the vessels

Sides effects and adverse reactions of ?:

– Common side effects of amlodipine and nifedipine: flushing, headache, ankle edema, palpitation

Sides effects and adverse reactions of Calcium Channel Blockers:

– ? commonly causes constipation, and less often bradycardia, heart block and cardiac failure

Warnings of Calcium Channel Blockers:

– ? are avoided in people with AV nodal conduction delay;

Warnings of Calcium Channel Blockers:

– ? are avoided in unstable angina

Warnings of ?:

• Avoid in renal artery stenosis and during pregnancy as it reduces placental blood flow

• Combination with potassium sparing diuretics-> risk of hyperkalemia

• Combination with NSAID-> risk of renal failure

are used in the treatment of acute angina

e.g. isosorbide dinitrate (Isordil) are used for prophylaxis of angina where beta blocker or CCB are insufficient

Contraindicated in client with severe aortic stenosis and haemodynamic instability

Used with caution in patients taking antihypertensive medication as it may precipitate hypotension

Clinical Manifestations of pancreatitis:

• Nausea and vomiting (caused by hypermotility or paralytic ileus secondary to pancreatitis or peritonitis)

• Abdominal distention accompanies bowel hypermotility and paralytic ileus and accumulation of fluids in peritoneal cavity (ascites)

Clinical Manifestations of pancreatitis:

• Pyrexia and leukocytosis

Clinical Manifestations of pancreatitis:

• Transient hyperglycemia if glucagon is released from damaged alpha cells in pancreatic islets

Clinical Manifestations of pancreatitis:

• Due to pancreatic oedema and blockage of CBD by inflammatory exudate

Clinical Manifestations of pancreatitis:

• Secondary to ascites and diaphragmatic irritation

Clinical Manifestations of pancreatitis:

• Plasma is lost as inflammatory mediators released into the circulation and this increase vascular permeability and dilate blood vessels.

• Hypovolemia can decrease renal blood flow and impair renal function

Clinical Manifestations of pancreatitis:

• Calcium is deposited in areas of fat necrosis

Clinical manifestations of Duodenal Ulcer:

• Chronic intermittent pain in epigastric area

• Pain begins ? hours after eating, when stomach is empty

• Pain relieved rapidly by ingestion of food or antacids (Pain-food-relief pattern)

?, Mechanism of action:

• Act by blocking the enzyme responsible for secreting hydrochloric acid in the stomach

• It binds irreversibly to H+,K+-adenosine triphosphatase (ATPase; proton pump), the enzyme that acts as a pump to release acid onto the surface of the gastrointestinal mucosa

Proton pump inhibitors, Adverse effects:

Omeprazole and other PPIs increase the risk for community- acquired and hospital-acquired pneumonia. Possible causes include alteration of upper GI flora (because of reduced gastric acidity) and impairment of white blood cell function.

Proton pump inhibitors, Adverse effects:

Long-term therapy, especially in high doses, increases the risk for osteoporosis and fractures by reducing acid secretion, which may decrease absorption of calcium.

Complications of Urinary Tract Obstruction:

• Upper urinary tract obstruction causes increased hydrostatic pressure, dilation of ureter, renal pelvis, calyces and renal parenchyma proximal to the site of obstruction

• The increased pressure in renal pelvis is transmitted to glomerulus, ↓ glomerular blood flow, ↓ glomerular filtration rate (GFR)

Complications of Urinary Tract Obstruction, Renal Damage:

(enlargement of renal pelvis and calyces)

Complications of Urinary Tract Obstruction, Renal Damage:

(accumulation of urine in ureter) occurs when obstruction affects outflow of urine from the distal ureter

Complications of Urinary Tract Obstruction, Renal Damage:

dilation of both the ureter and pelvis-calyceal system

Risk Factors of urinary tract stones:

1. Age

2. Male gender

3. Inadequate fluid intake

4. Occupation

5. Obesity

6. Physical inactivity

Categories of Diuretics:

Hydrochlorothiazide (Dichlotride)

Methyclothiazide (Enduron)

Categories of Diuretics:

Furosemide (Lasix)

Bumetanide (Burinex)

Categories of Diuretics:

Spironolactone (Aldactone)

Categories of Diuretics:

Mannitol

Categories of Diuretics:

Acetazolamide (Diamox)

Sites of Action of the Diuretics:

Act on the early distal tubule to block the reabsorption of sodium, chloride, and water. Excretion of potassium is increased

Sites of Action of the Diuretics:

Act on the ascending limb of the loop of Henle to block the reabsorption of sodium, chloride, and water. Excretion of potassium is increased

Sites of Action of the Diuretics:

Act on the late distal tubule and collecting ducts to block the reabsorption of sodium and reduce the secretion of potassium (sodium-potassium exchange). Excretion of potassium is not increased

Sites of Action of the Diuretics:

Act on the the proximal tubule and the loop of Henle to create an osmotic force that pulls water into the nephron and increase the excretion of nearly all electrolytes

Sites of Action of the Diuretics:

Inhibit reabsorption of bicarbonate ion in proximal tubule

• A chronic, complex and common endocrine disorder affecting 5-10% women of reproductive age with unclear etiology

• A heterogeneous condition, where multifactorial causes interact with endocrine, metabolic, genetic, and environmental factors

• Characterised by 3 main features: 1) irregular ovulation; 2) androgens excess; 3) polycystic ovary (at least two of them)

• Women with PCOS often present in their adolescence or early adulthood with symptoms of oligomenorrhoea, hirsutism or infertility

What is the disease?

Polycystic Ovary Syndrome, Disorder of Gonadotropin Release:

• Elevated ? secretion by the ovaries contributes to persistent anovulation

Polycystic Ovary Syndrome, Disorder of Gonadotropin Release:

• Persistent anovulation causes enlarged polycystic ovaries characterised by a smooth, pearly ? capsule

Inflammation of the prostate gland can be classified into:

I) Acute Bacterial Prostatitis

II) Chronic Bacterial Prostatitis

III) Chronic Pelvic Pain Syndrome

A. Inflammatory

B. Non-inflammatory

IV) Asymptomatic Inflammatory Prostatitis

The Ascending Pain Pathway:

? are thicker and are myelinated

The Ascending Pain Pathway:

? are thinner and non-myelinated.

The Ascending Pain Pathway:

Aδ fibers transmit pain impulses faster than C fibers

• ? is a condition characterized by thickening and hardening of the blood vessel

• Atherosclerosis is a form of ? that is caused by the accumulation of lipid-laden macrophages within the arterial wall, which leads to the formation of a lesion called a plaque

• is not a single disease but rather a pathologic process that can affect vascular systems throughout the body, resulting in ischemic syndromes

• is an inflammatory disease that develops and proceeds in the presence of elevated plasma cholesterol levels

• ? is a leading cause of death worldwide

• It refers to the heart disease caused by impaired coronary blood flow

• Common cause: atherosclerosis

• can cause:

– Angina

– Myocardial ischaemia

– Myocardial infarction (heart attack)

– Cardiac dysrhythmia

– Conduction defects

Pathophysiology of HFrEF:

• When contractility is ?, stroke volume falls and left ventricular end-diastolic volume

(LVEDV) ? -> dilation of heart and increase preload

Pathophysiology of HFrEF:

• ? preload stretch the heart which improve CO to a certain point

• Continuous dilation of myocardium eventually leads to dysfunction of sarcomeres and decrease contractility. This relationship is described by Frank-starling law of the heart

Pathophysiology of HFrEF:

• ? peripheral vascular resistance (PVR) in HT resulted in ? afterload

Pathophysiology of HFrEF:

• Sustained afterload resulting remodeling and hypertrophic cardiomyopathy -> ?

oxygen consumption leading to a state of relative ischemia and ? CO

Pathophysiology of HFrEF:

• ? CO diminish renal perfusion which activate RAAS

Pathophysiology of HFrEF:

• Activated RAAS increase PVR and plasma volume -> further ? preload and afterload

Symptoms:

1. Paroxysmal Nocturnal Dyspnea

2. Elevate Pulmonary Capillary Wedge Pressure

3. Pulmonary Congestion: Cough, Crackles, Wheezes, Blood-Tinged Sputum, Tachypnea

4. Restlessness

5. Confusion

6. Orthopnea

7. Tachycardia

8. Exertional Dyspnea

9. Fatigue

10. Cyanosis

Symptoms:

1. Fatigue

2. Increase Peripheral Venous Pressure

3. Ascites

4. Enlarged Liver & Spleen

5. May be seondary to chronic pulmonary problems

6. Distended Jugular Veins

7. Anorexia & Complaints of GI Distress

8. Weight gain

9. Dependent Edema

Centrally acting alpha2 agonists:

Side effects and adverse reaction:

• Drowsiness, dry mouth, dizziness, bradycardia

• High doses of methyldopa can cause sodium and water retention -> peripheral oedema

• Rebound hypertensive crisis can result if abruptly discontinued

Angiotensin II Receptor Blockers (ARBs):

• ARBs have similar effects to ACE inhibitors, they block the action of angiotensin II on the angiotensin I (AT1) receptors

found in many tissues

• ARBs are generally used when ACE inhibitors are not tolerated

• ARBs less likely cause dry cough and angioedema as they do not inhibit ACE

Pathophysiology of ?:

1. Functional liver tissue gradually destroyed and replaced by fibrous scar tissue

2. As hepatocytes and liver lobules are destroyed, metabolic functions of the liver are lost

3. Structurally abnormal nodules encircled by connective tissue develop

4. This fibrous connective tissue forms constrictive bands that disrupt blood and bile flow within liver lobules

5. Blood no longer flows freely through the liver to the inferior vena cava � increase pressure in portal venous system TEN

Pathophysiology of ?:

• In obstructive disease, backup of pancreatic secretions causes activation and release of enzymes (activated trypsin activates chymotrypsin, lipase and elastase) within pancreatic acinar cells.

• Activated enzymes cause autodigestion of pancreatic tissues, resulting in inflammation.

• Autodigestion causes vascular damage, coagulative necrosis, fat necrosis and formation of pseudocysts (walled-off collections of pancreatic secretions).

• Oedema within the pancreatic capsule leads to ischaemia and can contribute to necrosis.

• Recurrent inflammation activates pancreatic stellate cells become activated, causing pancreatic fibrosis, strictures, duct obstruction

and leading to chronic

Pathophysiology of ?:

• Small bowel obstruction is caused by postoperative adhesion, tumours, Crohn disease and hernias

• Distention caused by impaired absorption and increased secretion with accumulation of fluid and gas inside the lumen proximal to the obstruction

• Distention decreases the intestine’s ability to absorb water and electrolytes and increase the net secretion of these substances into the lumen

• Copious vomiting or sequestration of fluids in the intestinal lumen prevents their reabsorption and produces severe fluid and electrolyte disturbances

• Extracellular fluid volume and plasma volume decrease, causing dehydration, increased haematocrit level, hypotension and tachycardia

• Severe dehydration leads to hypovolemic shock

• Metabolic alkalosis initially develops as a result of excessive loss of hydrogen ions that would normally be reabsorbed from the gastric juice and vomiting

• With prolonged obstruction or obstruction lower in the intestine, metabolic acidosis occur because bicarbonate from pancreatic secretions and bile cannot be reabsorbed

• Hypokalaemia from vomiting and decreased potassium absorption can be extreme, promote acidosis and atony of intestinal wall

• Metabolic acidosis may also be accentuated by ketosis, the result of declining carbohydrate stores caused by starvation

• Lack of circulation permits the buildup of significant amounts of lactic acid

• If pressure form distention is severe enough, it occludes arterial circulation and cause ischaemia, necrosis, perforation and peritonitis

• Fever and leukocytosis are associated with overgrowth of bacteria and bowel necrosis

• Bacterial proliferation and translocation across the mucosa to the systemic circulation cause peritonitis or sepsis

• Large bowel obstruction is less common and often related to cancer

Pathophysiology of ?:

• Inflammation of the peritoneal membranes may commence with the presence of chemical irritants, such as bile, chyme, or foreign objects in the peritoneal cavity.

• This inflammation then increases the permeability of the intestinal wall, permitting enteric bacteria to enter the peritoneal cavity.

• Initially when local inflammation develops in the abdominal cavity, the peritoneum and omentum tend to produce a thick, sticky exudate, which helps the adjacent tissues to stick together

• This local inflammation may also reduce peristalsis in the area.

• However, unless the original cause of the problem is removed, it is likely that the inflammation or infection will spread.

• Abdominal distention is evident, and the typical rigid, boardlike abdomen develops as reflex abdominal muscle spasm occurs in response to involvement of the parietal peritoneum.

• Whatever the cause, this membrane is rapidly involved in the inflammatory response, which leads to vasodilation and increased permeability.

• The many blood vessels in the membranes can leak large volumes of fluid into the peritoneal cavity. Hypovolemic shock results

• The fluid, protein, and electrolytes sequestered in the peritoneal cavity are not recycled into the circulating blood

• This fluid becomes purulent as infection spreads.

• Nausea and vomiting, resulting from the intestinal irritation and pain, add to the fluid loss.

Manifestations of ?:

• abdominal pain occurs with localized tenderness

• Vomiting

• dehydration and hypovolemia

• Decreased skin turgor

• Dry buccal mucosa

• Pallor

• Low blood pressure

• tachycardia

• Fever and leukocytosis

Pathophysiology of ?:

1. Inflammation at the base of the crypts of Lieberkuhn in the large intestine

2. Disease begin in rectum and may extend proximally to the entire colon

3. Mucosa is inflamed and is involved in a continuous fashion

4. Small erosions form and coalesce into ulcers

5. Abscess formation, necrosis and ragged ulceration of the mucosa ensue

6. Edema and thickening of the muscularis mucosae may narrow the lumen of the involved colon

7. Mucosal destruction and inflammation causes bleeding, cramping pain and urge to defecate

8. Frequent diarrhoea with passage of small amounts of blood and purulent mucus

9. Loss of absorptive mucosal surface and rapid colonic transit time cause large volumes of watery diarrhoea

Clinical Manifestations of ?:

• Sever forms may involve the entire colon and characterized by abdominal pain, fever, an elevated pulse rate, frequent diarrhoea (10 – 20 stools /day), urgency, obviously blood stools and continuous crampy pain

• Dehydration, weight loss, anaemia and fever result from fluid loss, bleeding and inflammation

Proton pump inhibitors (PPIs), Therapeutic use:

therapy of duodenal ulcers, gastric ulcers, erosive esophagitis, and GERD

Proton pump inhibitors (PPIs), Therapeutic use:

therapy of hypersecretory conditions (e.g., Zollinger-Ellison syndrome).

Proton pump inhibitors, Administration alert:

• Because proton pump is activated by food intake, PPI should be taken ? minutes before the first major meal of the day

Osmotic (Saline) Laxatives:

another saline laxative that is not absorbed, draws water into the intestines to form a soft stool. It decreases the serum ammonia level and is useful in liver diseases, such as cirrhosis.

Osmotic (Saline) Laxatives:

acts like lactulose, increasing water in the faeces in the large intestine. The bulk that results from the increased water in the faeces stimulates peristalsis and defecation.

Side effects and adverse reactions

• Adequate renal function is needed to excrete excess magnesium. Patients who have renal insufficiency should avoid magnesium salts. Hypermagnesemia can result from continuous use of magnesium salts, causing symptoms such as drowsiness, weakness, paralysis, complete heart block, hypotension, flush, and respiratory depression.

• The side effects of excess lactulose use include flatulence, diarrhoea, abdominal cramps, nausea, and vomiting. Patients who have diabetes mellitus should avoid lactulose because it contains glucose and fructose.

Opiates and opiate-related agents:

• An opiate that has less potential for causing drug dependence than other opiates such as codeine.

• At higher doses, anticholinergic effects of atropine (e.g. drowsiness, dry mouth and tachycardia) will be experienced

Mechanism of action:

• Slows peristalsis, allow time for additional water reabsorption from the colon and more solid stools

• act by coating the wall of the GI tract and adsorbing bacteria or toxins that cause diarrhoea.

• include kaolin and pectin.

• Bismuth subsalicylate is considered an adsorbent because it absorbs bacterial toxins. Bismuth subsalicylate is an OTC drug commonly used to treat travelers’ diarrhoea, and it can also be used as an antacid for gastric discomfort.

Risk factors:

1. Primary causes:

• Minimal change disease (lipoid nephrosis)

• Membranous and focal segmental glomerulonephritis

2. Secondary causes:

• occur in systemic diseases including diabetes mellitus, amyloidosis, systemic lupus erythematosus and IgA vasculitis.

3. Certain drugs (e.g. nonsteroidal anti-inflammatory drugs)

4. Infections

5. Malignancies

6. Vascular disorders

1. Inflammation of the glomeruli

2. Oliguria

3. Cola-colored urine (Hematuria)

4. Berger's disease (IgA nephropathy) is the most common cause of primary glomerulonephritis

1. Hypoalbuminemia

2. Hyperlipidemia

3. Peripheral edema

4. Massive protenuria

1. Injury to podocytes

2. Podocyte dysfunction

1. Inflammatory response, damage glomerular basement membrane (GBM)

2. Podocyte attack by antibodies

● Results from damage to the glomeruli leading to dysfunction.

● Defined by the presence of:

○ heavy proteinuria (protein excretion greater than 3.5 g/ 24 hours),

○ hypoalbuminemia (less than 3.5 g/dL),

○ and peripheral edema.

● Associated with inflammatory response at the glomeruli leading to focal or diffuse lesions.

● In focal glomerulonephritis:

○ Asymptomatic hematuria and proteinuria are commonly seen .

○ or, occasionally, with episodes of gross hematuria.

● In diffuse glomerulonephritis:

○ Occur in more advanced disease.

○ The patient usually presents with heavy proteinuria (which may be in the nephrotic range), edema, hypertension , and kidney function impairment

Polycystic Ovary Syndrome, Clinical Manifestations:

1. Acanthosis nigricans

2. Hormonal disturbance:↑insulin, ↑androgen, ↑prolactin, ↑leptin, ↑LH, ↓SHBG

3. Obesity

4. Subfertility/ Infertility

Menopause:

• Natural menopause is defined as “permanent cessation of menstruation resulting from loss of ovarian follicular function” and is recognized after consecutive ? months of amenorrhoea without obvious physiological or pathological causes

• The ovarian response to elevated LH levels by recruiting more follicles, but these follicles only partially develop, resulting in irregular ovulation, lower progesterone levels, depleted follicle reserve and infertility

• The increase in anovulatory cycles allows the endometrium to grow thicker and may lead to dysfunctional uterine bleeding

Changes in Hormones and Around Menopause:

• The increase in anovulatory cycles allows the endometrium to grow thicker and may lead to dysfunctional uterine bleeding

• Ovaries shrink and uterus undergoes atrophy; the cervix and vagina become pale and friable; decrease in vaginal lubricant and increase in vaginal pH increase the risk of tear, bleeding and infection

• Labia majora and minora become less prominent; some pubic hair is lost

• Urethral tone declines with decreased muscle tone throughout the pelvic area -> increased risk of urinary incontinence

Changes in Hormones and Around Menopause:

• The breasts become pendulous with a decrease in tissue mass, leaving only the ducts, fat and connective tissue -> decrease in size and firmness

• Loss of cyclic mastalgia (breast pain)

Changes in Hormones and Around Menopause:

• Accelerated bone loss -> reduce bone mass -> higher risk of osteoporosis and fracture

Changes in Hormones and Around Menopause:

• Altered lipid metabolism -> increased LDL and total cholesterol levels, decreased HDL level; increased risk for metabolic syndrome & atherosclerosis

• Accelerated vascular ageing -> endothelial dysfunction and large artery stiffening

Changes in Hormones and Around Menopause:

• Systemic changes: Vasomotor symptoms (hot flush, night sweat) related to loss of negative feedback over hypothalamic noradrenaline (involves in thermoregulation) production secondary to low oestrogen levels and the relative increase in other hormones e.g. LH, FSH

Prostatitis:

• A sub-type of UTI, mostly likely caused by an ascending urethral infection or reflux of infected urine into the prostatic ducts

• Escherichia coli is the most common causative organism; other gram-negative bacteria may also be the pathogenic agent e.g. Klebsiella, Pseudomonas

• May be acute and unrelated to previous illness; or may follow urinary catheterization or cystoscopy

• Infection stimulates an inflammatory response in which the prostate becomes enlarged, tender, firm or boggy

• The bacteria is present in the exudate of moist mucosa or cutaneous lesions; human is its only natural host

• Infection is usually transmitted through abrasion during sexual intercourse but can also occur extragenitally

• The disease is divided into primary, secondary, latent and tertiary stage, with Incubation period from 12 days to 12 week after exposure

• All stages of syphilis in pregnant women pose a risk of transmission to the foetus, but it is higher with early stages than with the later ones

• Each stage is associated with different signs and symptoms

Syphilis:

• Occurs 3-12 weeks after resolution of a chancre; the infection spreads to all major organ systems by haematogenous dissemination of spirochete, and the disease becomes systemic

• The most recognised clinical syndrome of syphilis, mostly among females or MSM (men having sex with men)

• This stage is followed by a period during which the immune system is able to suppress the infection

Syphilis:

• Follows the untreated secondary stage; absence of visible signs and symptoms

• The infection can only be detected by serological testing; transmission is possible during this stage

• Early latent stage can occur between the primary and secondary stages or after the resolution of secondary stage

• It may last for life or progress to tertiary stage; the individual may be infective during the first 1 to 2 years of latency

Syphilis:

• A delayed response to untreated infection and affect different body systems

• The most severe stage of the disease with high morbidity and mortality

• The destructive skin, bone and soft tissue lesions (gummas) of tertiary syphilis are caused by severe hypersensitivity reaction to the microorganism

• The bacteria can damage the nervous system, and lead to neurosyphilis; involvement of cardiovascular system may cause aneurysms, heart valve insufficiency and heart failure

• May occur 10–30 years after the infection began

Syphilis:

• Transmitted from the mother to the foetus by vertical transmission

• It becomes a systemic disease shortly after maternal infection because the spirochete can pass through the placenta

• If the infection is transmitted within the first trimester of pregnancy, the consequences may include premature delivery, spontaneous abortion, stillbirth, nonimmune hydrops, or perinatal death

• The risk of congenital syphilis is the highest in primary syphilis and decreases with advancing stage of the disease

Clinical Manifestations:

• Passage of spirochete across the placenta can affect any or all foetal tissues

• Can cause foetal death or growth abnormalities, including changes in foetal bones, teeth, and ne through the placenta urological system

• A variety of manifestations can be found in the affected newborns, including growth abnormalities, rashes, hepatosplenomegaly, jaundice, CNS involvement , including blindness and deafness

Classification of Fractures:

⮚ A concurrent break in the area of the fracture

⮚ Complicated by infection, osteomyelitis, delayed union, non-union

Classification of Fractures:

⮚ No break in the surrounding skin

Classification of Fractures:

⮚ The bone is damaged but still in 1 piece

Classification of Fractures:

⮚ The integrity of the bone is broken into 2 pieces

Classification of Fractures:

⮚ A slanted angle to the shaft of the bone

Classification of Fractures:

⮚ Encircles the bone

Classification of Fractures:

⮚ Occurs straight across the bone

Classification of Fractures:

⮚ Perforates one cortex and splinters the spongy bone

Classification of Fractures:

• A break at the site of a pre-existing abnormality

Classification of Fractures:

• The bone breaks into more than 2 fragments

Bone healing:

• It develops from torn blood vessels in the periosteum and adjacent muscles and soft tissue

• Fibrin and platelets within the hematoma form a meshwork -> the initial framework for healing with the help of hematopoietic growth factors

Bone healing:

• Fibroblasts, capillary buds and osteoblasts move into the wound to produce granulation tissue called procallus

• Cartilage is formed

• Type I, II, III collagen are formed

Bone healing:

• Osteoblasts in the procallus form membranous / woven bone (callus)

• Enzymes increase the phosphate content and permit the phosphate to join with calcium -> deposited as mineral to harden the callus

Bone healing:

• Basic multicellular units of the callus are replaced with lamellar bone or trabecular bone

Bone healing:

• The periosteal and endosteal surfaces of the bone are remodeled -> the size and shape of the bone before injury

• It is vital for good mechanical properties for weight bearing and mobility

Factors influencing bone healing:

• Immobilization

• Timely correction of displacement

• Application of ice

• Electrical stimulation

Factors influencing bone healing:

• Adequate amounts of growth hormone, vitamin D and calcium

• Adequate blood supply

• Absence of infection or diseases

• Younger age

• injury

Factors influencing bone healing:

• Delay in correction of displacement

• Open fracture

• Presence of foreign body at fracture site

Factors influencing bone healing:

• Immunocompromised status

• Decrease circulation (DM, PVD)

• Malnutrition

• Osteoporosis

• Advanced age

• Degenerative, Non-infective inflammatory joint disease

• Is the most common form of joint disease and leading cause of disability in middle-age and old population

• Characterized by:

⮚ Local areas of loss and damage of articular cartilage,

⮚ new bone formation of joint margins (osteophytosis),

⮚ subchondral bone changes,

⮚ variable degree of mild synovitis and

⮚ thickening of the joint capsule

• a chronic, systemic, inflammatory autoimmune disease

• Involve many tissues and organs but particularly affect joints

• Involve synovial inflammation, joint swelling and ankylosis and destruction of articular cartilage

• The initiating mechanism of RA is still unknown

• likely a combination of genetic factors and environmental factors

• Inflammatory response to excessive quantities of uric acid (hyperuricemia) in the blood and in other body fluids  formation of monosodium urate (MSU) crystal in and around joints

• Crystallization in synovial fluid is acute, painful inflammation of the joint

• Prolonged accumulation results in joint damage -> gouty arthritis

• Crystal deposition in subcutaneous tissues -> small, white nodules/ tophi, which visible through the skin

• Severe pain

• Location:

⮚ Metatarsophalangeal joint of great toe, heel, ankle and the instep of foot, knee, wrist or elbow

• Red, hot, swollen and tender joint

• Fever, chills, malaise

1. an increase in the serum urate concentration (hyperuricemia)

2. recurrent attacks of monoarticular arthritis (inflammation of a single joint)

3. deposits of MSU monohydrate (tophi) in and around the joints

4. renal disease involving glomerular, tubular, and interstitial tissues and blood vessels and

5. the formation of renal stones.

Clinical manifestation of osteoarthritis:

• most predominant symptom

• appear during the fifth or sixth decade of life;

• Pain in one or more joints-usually with weight bearing, use of the joint, or load bearing

• Resting the joint often relieves pain.

• Nocturnal pain is usually not relieved by rest and may be accompanied by paresthesias (numbness, tingling, or prickling sensations).

Clinical manifestation of osteoarthritis:

• usually occurs as joint movement begins, and it dissipates rapidly after a few minutes. Stiffness lasting longer than 30 minutes is uncommon in OA.

• Joint motion is accompanied by sounds of crepitus, creaking, or grating.

Clinical manifestation of osteoarthritis:

• Due to inflammation of the joint lining, known as synovitis

• inflammation cause inflammatory exudate or blood enters the joint

Clinical manifestation of osteoarthritis:

• caused by bone enlargement or the proliferation of osteophytes around the margins of the joint.

Clinical manifestation of rheumatoid arthritis (RA):

• Fever

• Fatigue

• Weakness

• Anorexia

• Weight loss

• Generalized aching and stiffness

Clinical manifestation of rheumatoid arthritis (RA):

• Inflammation may be apparent first in fingers/ wrists, affects joints in a symmetric fashion, usually more than 1 pair of joints is involved

• Joints appear red & swollen

• Painful with touch

• Joint stiffness

• Impaired joint movement

Clinical manifestation of gout, The manifestations appear in three clinical stages:

↑serum urate level, but arthritic symptoms, tophi, and renal stones are not present

Clinical manifestation of gout, The manifestations appear in three clinical stages:

Attacks develop with increased serum urate concentrations; tends to occur with sudden or sustained increases of hyperuricemia/ triggered by trauma, drugs, and alcohol

Clinical manifestation of gout, The manifestations appear in three clinical stages:

Chronic stage; can begin as early as 3 years to 40 years after the initial attack of gouty arthritis. Progressive inability to excrete uric acid expands the urate pool until MSU crystal deposits (tophi) appear in cartilage, synovial membranes, tendons, and soft tissue.

The Ascending Pain Pathway:

travel from the nociceptors to the spine

The Ascending Pain Pathway:

travel upwards through the spinal cord towards the thalamus in the brain

The Ascending Pain Pathway:

run from the thalamus through the brain towards the somatosensory area of the cerebral cortex

Diphenhydramine HCL (Benadryl)

Action:

• similar to chlorpheniramine maleate

Uses:

• Allergy symptoms, allergic rhinitis

• Nonproductive cough

• Motion sickness

• Insomnia in children

• Hypersensitivity reactions, including anaphylaxis and transfusion reactions

• Mild form of Parkinson’s disease (anticholinergic action to treat tremor and restlessness)

Loratadine (Clarityne)

Action:

• Binds (selectively) to peripheral histamine receptor, thereby providing antihistamine action without sedation

Uses:

• Allergy symptoms, seasonal rhinitis

• Urticaria

Side-effects:

• Headache, fatigue, restlessness

• Dry mouth

• Sedation (more common with increased doses)

Pharmacokinetics:

• Onset 1-3 hours, peak 8-10 hours and duration 24 hrs

• Metabolized in liver to active metabolites and excreted in urine

Side-effects:

Side-effects:

• similar to chlorpheniramine maleate

Pharmacokinetics:

• Peak 2 – 4 hrs and duration 4 – 8 hrs (oral)

• Metabolized in liver, excreted by kidneys

• Crosses placenta, excreted in breast milk

• Cyclooxygenase (COX) is the enzyme responsible for converting arachidonic acid into prostaglandins and their products

• Cyclooxygenase has two enzyme forms:

• COX- 1 and COX-2

• Drugs that block an opioid receptor

• They are used to reverse symptoms of opioid addiction, toxicity and overdose (include sedation or respiratory distress)

Naloxone (Narcan)

Opioid analgesic:

- Drugs that stimulate/ activate a particular opioid receptor (both mu(μ) and kappa (κ) receptors )

- E.g. morphine and codeine

Opioid analgesic:

- Drugs that block both mu and kappa receptors

- E.g. Naloxone (Narcan)

Opioid analgesic:

- Drugs that occupy one receptor and block on the other

- E.g. Pentazocine (Talwin)

Suxamethonium chloride (Succinylcholine)

Neostigmine

General Anaesthesia:

1. nitrous oxide

2. Sevoflurane (Ultane)

3. Desflurane (Suprane)

General Anaesthesia:

1. Propofol (Diprivan)

2. Etomidate (Amidate)

3. Thiopental Sodium (Pentothal)

4. Ketamine hydrochloride (Ketalar)

5. Dexmedetomidine (Precedex)

Clinical Manifestations of pancreatitis, Pain:

May radiates to the ? (due to retroperitoneal location of pancreas)