INFARCTION

 An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue 

 Nearly 99% of all infarcts result from thrombotic or embolic events 
 
other mechanisms include: local vasospasm, expansion of an atheroma, extrinsic compression of a vessel (e.g., by tumor); vessel twisting (e.g., in testicular torsion or bowel volvulus; and traumatic vessel rupture

MORPHOLOGY OF INFARCTS 

 infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or aseptic 

 All infarcts tend to be wedge-shaped, with the occluded vessel at the apex and the periphery of the organ forming the base 
 
 The margins of both types of infarcts tend to become better defined with time 
 
 The dominant histological characteristic of infarction is ischemic coagulative necrosis 
 
 most infarcts are ultimately replaced by scar. The brain is an exception, it results in liquefactive necrosis 
 
 RED INFARCTS:
occur in 
(1) venous occlusions (such as in ovarian torsion) 
(2) loose tissues (like lung) that allow blood to collect in the infarcted zone 
(3) tissues with dual circulations (lung and small intestine) 
(4) previously congested tissues because of sluggish venous outflow 
(5) when flow is re-established to a site of previous arterial occlusion and necrosis 

WHITE INFARCTS 

occur with: 
1) arterial occlusions 
2) solid organs (such as heart, spleen, and kidney).

Septic infarctions - occur when bacterial vegetations from a heart valve embolize or when microbes seed an area of necrotic tissue. - the infarct is converted into an abscess, with a correspondingly greater inflammatory response

FACTORS THAT INFLUENCE DEVELOPMENT OF AN INFARCT
- nature of the vascular supply 
- rate of development of the occlusion (collateral circulation ) 
- vulnerability to hypoxia - Neurons undergo irreversible damage 
- 3 to 4 minutes of ischemia. - Myocardial cells die after only 20 to 30 minutes of ischemia 
- the oxygen content of blood
 

Infections caused by gonorrhea

1.  Acute urethritis.  Mostly in males.  Generally self-limiting.  Dysuria and purulent discharge.

2.  Endocervical infection.  Purulent vaginal discharge, abnormal menses, pelvic pain.  Often co-infection with other STD’s.  Some women are asymptomatic.

3.  Pelvic Inflammatory Disease (PID).  Consequence of ascending endocervical infection.  Causes salpingitis, endometriosis, bilateral abdominal pain, discharge, fever.  May lead to sterility, chronic pain, and ectopic pregnancy because of loss of fallopian cilia.

4.  Anorectal inflammation.  Mostly in homosexual men.  Pain, itching, discharge from anus.

5.  Dermatitis/arthritis.  Occurs after bacteremia.  Skin will have papules on an erythematous base which develop into necrotic pustules.  Asymmetric joint pain.  These infections are susceptible to penicillin.

6.  Neonatal infections.  Ophthalmia neonatorum is a conjunctival infection from going through infected vagina.  After one year of age, suspect child abuse.

ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological

- Foetal involution.
    o    Branchial clefts.
    o    Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
    o    Post-partum uterus.
    o    Post-menopausal ovaries and uterus
    o    Post-lactational breast
    o    Thymus.
(2) Pathological:
- Generalised as in

    o    Ageing.
    o    Severe starvation and cachexia
- Localised :
    o    Disuse atropy of bone and muscle.
    o    Ischaemic atrophy as in arteriosclerotic kidney. .
    o    Pressure atrophy due  to tumours and of kidney in hydronephrosis.
    o    Lack of trophic stimulus to endocrines and gonads.
 

Summary 
Hepatitis A → ssRNA → Picornavirus → Oral–anal
Hepatitis B → dsDNA → Hepadnavirus → Sexual contact , Blood (needles), Perinatal
Hepatitis C → ssRNA → Flavivirus → Sexual contact , Blood (needles)
Hepatitis D → ssRNA → Deltavirus → Sexual contact, Blood (needles)
Hepatitis E → ssRNA → Calicivirus → Oral–anal 

Nephrotic Syndrome
The patient will present with a triad of symptoms:
- Proteinuria, i.e. >3g/24hr-3.5g/24 hr
- Hypoalbuminaemia, i.e. <30g/L
- Oedema 
 >80% of cases are due to glomerulonephritis. In this syndrome, there is damage to podocytes 
 
 Clinical signs
- Pitting oedema, particularly in the limbs and around the eyes; may also cause genital oedema and ascites.
- Possible hypertension 

Causes
- Primary causes – these are diagnoses of exclusion that are only made if secondary causes cannot be found
    o Minimal change disease (MCD)
    o Focal segmental glomerulosclerosis
    o Membranous nephropathy
- Secondary causes – note that these fall into the same three categories as above:
    o Minimal change disease – Hep B, SLE, diabetes M, sarcoidosis, syphilis, malignancy
    o Focal segmental glomerulosclerosis –HIV, obesity, diabetes M, hypertensive nephrosclerosis
    o Minimal change disease –drugs, malignancy, particularly Hodgkin’s lymphoma  
    
 - Differential diagnoses include cardiac failure, i.e. increased JVP, pulmonary oedema and mild proteinuria, and liver disease, i.e. reduced serum albumin.
- The condition causes an increased susceptibility to infection – partly due to loss of immunoglobulin in the urine. Patients tend to be prone to streptococcus infection, as well as bacterial peritonitis and cellulitis.
- Nephrotic syndrome also increases the risk of thromboembolism and hyperlipidaemia.
- The former is due to an increase in the synthesis of clotting factors and to platelet abnormalities, and the latter is a result of increased synthesis of these by the liver to counteract reduced oncotic pressure.  

Investigations

- These are the same as those carried out in GN.
- Also, check for cholesterol as part of confirming the presence of hyperlipidemia.
- Renal biopsy – order this for all adults. In children, because the main cause is minimal change GN, steroids are the first-line treatment. Therefore, in children, biopsy is necessary only if pharmaceutical intervention fails to improve the situation.
- The hypercoagulant state seen in the nephrotic syndrome can be a risk factor for renal vein thrombosis. This can present as loin pain, haematuria, palpable kidney and sudden deterioration in kidney function. This should be investigated with Doppler USS, MRI or even renal angiography.
- Once diagnosed, give warfarin for 3 to 6 months.

Management

- Generally, this involves treatment of the underlying condition which is usually GN. Therefore, fluid management and salt intake restriction are priorities. The patient is usually given furosemide along with an ACE inhibitor and/or an angiotensin II receptor antagonist. Prophylactic heparin is given if the patient is immobile. Hyperlipidaemia can be treated with a statin. 

Nephritic Syndrome 

Acute and chronic
forms of the syndrome exist. The main difference between this and nephrotic syndrome is that in nephritic syndrome haematuria is present. There is also proteinuria, hypertension, uraemia, and possibly oliguria. The two standout features are hypertension and RBC casts. The urine will often appear ‘smoky’ in colour due to the presence of RBC casts. Very rarely, it may appear red 

Causes

1. Post-streptococcal
2. Primary:
- Membranous glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger’s disease)
3. Secondary
- HSP
- Vasculitis

Clinical Features

- Abrupt onset of :
    o Glomerular haematuria (RBC casts or dysmorphic RBC)
    o Non-nephrotic range proteinuria (< 2 g in 24 hrs)
    o Oedema (periorbital, sacral )
    o Hypertension
    o Transient renal impairment (oliguria, uraemia)
- Urinary casts – these are cylindrical structures produced by the kidney and present in the urine in certain renal diseases. They form in the DCT and collecting duct, dislodging and passing in the urine where they are detected by microscopy. RBC casts are usually associated with nephritic syndrome. The presence of RBCs within a cast is always pathologic and strongly indicative of glomerular damage.
- The proteinuria present is often smaller than in nephrotic syndrome, thus a coexistent condition of nephrotic syndrome is not usually present.
- Encepelopathy may be present, particularly in children, due to electrolyte imbalances and hypertension. This type of presentation is indicative of glomerular damage, but requires renal biopsy to determine the exact problem. In this respect it is similar to nephrotic syndrome.
Overlapping of the two syndromes is possible as nephrotic syndrome may precede nephritic syndrome, although not vice-versa.

Mechanisms of the syndrome vary according to cause; both primary and secondary causes exist. Post-infectious GN is the classic illustration of nephritic syndrome, but the condition may be caused by other glomerulopathies and by systemic diseases such as connective tissue disorders 

Two clinical terms to remember:
- Nephritic syndrome; which comprises edema, proteinuria, hypoalbuminemia, hematuria (smoky urine), oligurua and hypertension.
- Nephrotic syndrome; which comprises of albuminuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria. 

Joint pathology
1. Rheumatoid arthritis
a. Cause is autoimmune in nature.
b. More common in women aged 20 to 50.
c. Characterized by inflammation of the synovial membrane. Granulation tissue, known as pannus, will form in the synovium and expand over the articular cartilage. This causes the destruction of the underlying cartilage and results in fibrotic changes and ankylosis.
Scarring, contracture, and deformity of the joints may occur.
d. Clinical symptoms include swollen joints. It can affect any joint in the body.

2. Osteoarthritis
a. Most common arthritis.
b. Cause is unknown.
c. Higher incidence in women, usually after age 50.
d. Characterized by degeneration of the articular cartilage and the formation of osteophytes (bony spurs) at the margins of affected areas.
Clinical signs and symptoms include:
(1) Stiff and painful joints affecting joints in the hand (phalangeal joints) and weight-bearing joints.
(2) Heberden’s nodes—nodules at the distal interphalangeal joint.
(3) Bocard’s nodes—nodules at the proximal interphalangeal joint.